 Substituted benzopyran derivatives for the treatment of inflammation
专利摘要:
Benzopyran derivatives are described for use in treating cyclooxygenase-2 mediated diseases. Particularly interesting compounds are defined by formula (I ′), wherein X, A 1 , A 2 , A 3 , A 4 , R, R ″, R 1 and R 2 are as described in the detailed description. 公开号:KR20010020152A 申请号:KR1019997009710 申请日:1998-04-18 公开日:2001-03-15 发明作者:카터제프리에스.；오부코위츠마크쥐.；데바다스발레쿠드루；탤리존제이.；브라운데이빗엘.；그래니토매튜제이.；버텐쇼스티븐알.；로지어도날드제이.주니어；나가라얀스리니바산알.；하나우캐슬린이.；하트맨수잔제이.；루드윅신디엘.；메츠수잔 申请人:쥐.디. 씨얼리 앤드 컴퍼니； IPC主号:
专利说明:
Substituted benzopyran derivatives for the treatment of inflammation {SUBSTITUTED BENZOPYRAN DERIVATIVES FOR THE TREATMENT OF INFLAMMATION} Prostaglandins play an important role in the inflammatory process, and the production of prostaglandins, in particular PGG 2 , PGH 2 and PGE 2 , has become a common target for anti-inflammatory drug discovery. However, conventional bisteroidal anti-inflammatory drugs (NSAIDs) that are active in reducing prostaglandin-induced pain and edema associated with the corresponding inflammatory response are also active in the performance of other prostaglandin-modulating reactions not related to the inflammatory response. Thus, high doses of the most common NSAIDs can cause serious side effects that limit the potential of treatment, including life-threatening ulcers. Alternatives to NSAIDs are the use of corticosteroids, which have more severe side effects, especially when long-term treatment is involved. Conventional NSAIDs have been found to interfere with the production of prostaglandins by inhibiting enzymes in the human arachidonic acid / prostaglandin pathway, including the enzyme cyclooxygenase (COX). Recent findings of induction enzymes associated with inflammation (named "cyclooxygenase-2" or "prostaglandin G / H synthase II") have been shown to inhibit inflammation to reduce severe side effects while reducing inflammation more effectively. Provides a viable target of The following references describing anti-inflammatory activity demonstrate a continuing effort to find safe and effective anti-inflammatory agents. The novel benzopyrans, dihydroquinolines, benzothiopyrans, and dihydronaphthalene derivatives described herein are safe and efficient anti-inflammatory agents from this ongoing effort. The substituted benzopyrans, dihydroquinolines, benzothiopyrans and dihydronaphthalene derivatives disclosed herein preferably selectively inhibit cyclooxygenase-2 rather than cyclooxygenase-1. US Pat. No. 5,618,843 to Fisher et al. Generally describes bicyclic moieties substituted with acids as IIb / IIIA antagonists. WO 94/13659, issued June 23, 1994, describes fused benzo compounds for the treatment of CNS diseases. Manrao et al. (J. Indian. Counc. Chem., 12, 38-41 (1996)) describe carboxy coumarinimide derivatives and their antifungal activity. US Pat. No. 5,348,976 to Shibata et al. Describes amide substituted benzopyrans as antifungal agents. WO 96/40110, issued December 19, 1996, describes benzopyrans as tyrosine kinase modulators. Loiodice et al. (Tetrahedron, 6, 1001-11 (1995)) describe 6-chloro-2,3-dihydro-4H-1-benzopyran carboxylic acid. Clemence et al. (J. Med. Chem., 31, 1453-62, (1988)) describe 4-hydroxy-3-quinolinecarboxylic acid as starting material in the preparation of anti-inflammatory agents. Lazer et al. (J. Med. Chem., 40, 980-89 (1997)) describe benzothiopyran carboxylate as starting material in the preparation of anti-inflammatory agents. Benzopyran-3-carboxylic acid has already been described. Gupta et al. (Indian J. Chem., 21B, 344-347 (1982)) describe chromium-3-carboxylic acid as an intermediate in the preparation of centrally functional muscle relaxants. Rene and Royer (Eur. J. Med. Chem.-Chim. Ther., 10, 72-78 (1975)) describe a process for the preparation of chromen-3-carboxylic acid. U.S. Pat. No. 4,665,202 to Rimbault et al. Describes 2-phenyl substituted flabens and thioflavbenes as 5-lipoxygenase inhibitors. US Pat. No. 5,250,547 to Lochead et al. Describes benzopyran derivatives as 5-lipoxygenase inhibitors. Satoh et al. (J. Med. Chem., 36, 3580-94 (1993)) describe substituted chromenes as 5-lipoxygenase inhibitors. US Pat. No. 5,155,130 to Stanton et al. Describes substituted chromenes as 5-lipoxygenase inhibitors, in particular 6-benzyloxy-2H-benzopyran-3-carboxylic acid as intermediate. However, the compounds of the present invention have not been described as cyclooxygenase inhibitors. FIELD OF THE INVENTION The present invention relates to the field of anti-inflammatory pharmaceutical formulations and in particular to compounds, compositions and methods for treating cyclooxygenase-2 mediated diseases such as inflammation and inflammation-related diseases. A group of compounds useful for the treatment of cyclooxygenase-2-mediated diseases is defined by Formula I 'or an isomer or a pharmacologically acceptable salt thereof: Wherein X is selected from O, S, CR c R b and NR a ; Wherein R a is hydrido, C 1 -C 3 -alkyl, (optionally substituted phenyl) -C 1 -C 3 -alkyl, alkylsulfonyl, phenylsulfonyl, benzylsulfonyl, acyl and carboxy-C 1 -C 6 -alkyl; Wherein R b and R c are each hydrido, C 1 -C 3 -alkyl, phenyl-C 1 -C 3 -alkyl, C 1 -C 3 -perfluoroalkyl, chloro, C 1 -C 6 -alkyl Independently selected from thio, C 1 -C 6 -alkoxy, nitro, cyano and cyano-C 1 -C 3 -alkyl; Wherein CR c R b forms a cyclopropyl ring; Wherein R is selected from carboxyl, aminocarbonyl, C 1 -C 6 -alkylsulfonylaminocarbonyl and C 1 -C 6 -alkoxycarbonyl; Wherein R '' is selected from hydrido, phenyl, thienyl, C 2 -C 6 -alkynyl and C 2 -C 6 -alkenyl; Wherein R 1 is from C 1 -C 3 -perfluoroalkyl, chloro, C 1 -C 6 -alkylthio, C 1 -C 6 -alkoxy, nitro, cyano and cyano-C 1 -C 3 -alkyl Selected; Wherein R 2 is hydrido, halo, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, halo-C 2 -C 6 -alkynyl, aryl- C 1 -C 3 -alkyl, aryl-C 2 -C 6 -alkynyl, aryl-C 2 -C 6 -alkenyl, C 1 -C 6 -alkoxy, methylenedioxy, C 1 -C 6 -alkylthio , C 1 -C 6 -alkylsulfinyl, -O (CF 2 ) 2 O-, aryloxy, arylthio, arylsulfinyl, heteroaryloxy, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl , Aryl-C 1 -C 6 -alkyloxy, heteroaryl-C 1 -C 6 -alkyloxy, aryl-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl , C 1 -C 6 -haloalkoxy, C 1 -C 6 -haloalkylthio, C 1 -C 6 -haloalkylsulfinyl, C 1 -C 6 -haloalkylsulfonyl, C 1 -C 3- (halo Alkyl-C 1 -C 3 -hydroxyalkyl, C 1 -C 6 -hydroxyalkyl, hydroxyimino-C 1 -C 6 -alkyl, C 1 -C 6 -alkylamino, arylamino, aryl-C 1 -C 6 - alkylamino, heteroaryl, arylamino, heteroaryl, -C 1 -C 6 - alkylamino, nitro, cyano, amino, amido Alkylsulfonyl, C 1 -C 6 - alkylamino-sulfonyl, aryl sulfonyl amino, heteroaryl, aminosulfonyl, aryl, -C 1 -C 6 - alkyl, aminosulfonyl, heteroaryl, -C 1 -C 6 - alkyl-amino alcohol Ponyl, heterocyclylsulfonyl, C 1 -C 6 -alkylsulfonyl, aryl-C 1 -C 6 -alkylsulfonyl, optionally substituted aryl, optionally substituted heteroaryl, aryl-C 1 -C 6 -alkylcar Carbonyl, heteroaryl-C 1 -C 6 -alkylcarbonyl, heteroarylcarbonyl, arylcarbonyl, aminocarbonyl, C 1 -C 6 -alkoxycarbonyl, formyl, C 1 -C 6 -haloalkylcarbonyl And one or more radicals independently selected from C 1 -C 6 -alkylcarbonyl; and Wherein the A ring atoms A 1 , A 2 , A 3 , and A 4 are independently selected from carbon and nitrogen provided that at least two of A 1 , A 2 , A 3 and A 4 are carbon; Or R 2 together with ring A form a radical selected from naphthyl, quinolyl, isoquinolyl, quinolizinyl, quinoxalinyl and dibenzofuryl. A related group of compounds useful for treating cyclooxygenase-2 mediated diseases is defined by Formula I and its isomers or pharmacologically acceptable salts thereof; Wherein X is selected from O or S or NR a ; Wherein R a is alkyl; Wherein R is selected from carboxyl, aminocarbonyl, alkylsulfonylaminocarbonyl and alkoxycarbonyl; Wherein R 1 is selected from haloalkyl, alkyl, arylalkyl, cycloalkyl and aryl optionally substituted with one or more radicals selected from alkylthio, nitro and alkylsulfonyl; Wherein R 2 is hydrido, halo, alkyl, aralkyl, alkoxy, aryloxy, heteroaryloxy, arylalkyloxy, heteroaralkyloxy, haloalkyl, haloalkoxy, alkylamino, arylamino, aralkylamino, Heteroarylamino, heteroarylalkylamino, nitro, amino, aminosulfonyl, alkylaminosulfonyl, arylaminosulfonyl, heteroarylaminosulfonyl, arylalkylaminosulfonyl, heteroaralkylaminosulfonyl, heterocyclosulfonyl At least one radical selected from alkylsulfonyl, optionally substituted aryl, optionally substituted heteroaryl, aralkylcarbonyl, heteroarylcarbonyl, arylcarbonyl, aminocarbonyl, and alkylcarbonyl; Or wherein R 2 together with Ring A form a naphthyl radical. The compounds of the present invention are useful for, but are not limited to, treatment of inflammation in the human body and other cyclooxygenase-2 mediated diseases such as analgesics in the treatment of pain and headache, or antipyretics in the treatment of heat. For example, the compounds of the present invention are useful for the treatment of arthritis, including but not limited to rheumatoid arthritis, spinal arthritis, gouty arthritis, osteoarthritis, systemic lupus erythematous and juvenile arthritis. The compounds of the present invention may be used for asthma, bronchitis, menstrual cramps, preterm birth, tendonitis, bursitis, liver disease including hepatitis, skin-related diseases such as psoriasis, eczema, burns and dermatitis, and ophthalmic surgery such as cataract surgery and refractive surgery. It is useful for the healing of postoperative inflammation, including. The compounds of the present invention are also useful for treating gastrointestinal diseases such as inflammatory bowel disease, Crohn's disease, gastritis, irritable bowel symptoms and ulcerative colitis. Compounds of the present invention include migraine, nodular arthritis, thyroiditis, congenital anemia, Hodgkin's disease, seedling, rheumatic fever, type I diabetes, neuromuscular junction disease, including myasthenia gravis, brain leukemia including multiple seedlings, sarcoidosis ), Nephritis symptoms, Behcet's syndrome, polymyositis, gingivitis, nephritis, hypersensitivity, boils that occur after wounds, including brain edema, and inflammation in diseases such as myocardial ischemia. The present compounds are also useful for the treatment of eye diseases such as retinitis, conjunctivitis, retinal pain, uveitis, visual photophobia, and acute injury to ocular tissues. The compounds are also useful in the treatment of pulmonary inflammation, such as those associated with viral inflammation and cystic fibrosis. The compounds are also useful in the treatment of central nervous system diseases such as cortical dementia, including Alzheimer's disease, and central nervous system damage from seizures, ischemia and trauma. The compounds of the present invention are useful for the treatment of arthritis, with the added advantage of significantly reduced adverse side effects. These compounds are also useful for the treatment of allergic rhinitis, dyspnea symptoms, endotoxin shock symptoms, and liver disease. The compound is not limited to pain due to postoperative pain, toothache, muscle pain, and cancer, and is also useful for pain. The compound is also useful for the treatment of dementia. The term "treatment" includes complete or partial inhibition of dementia, including Alzheimer's disease, vascular dementia, multi-infarct dementia, premature dementia, alcoholic dementia, and senile dementia. The above methods are useful for the treatment and prevention of inflammation-related cardiovascular diseases of the human body, but are not limited to these diseases. The method includes vascular disease, coronary artery disease, aneurysm, arteriosclerosis including heart transplant atherosclerosis, myocardial infarction, embolism, seizures, thrombosis including venous thrombosis, angina such as unstable angina, coronary plaque inflammation, chlamydia- Bacterial-induced inflammation, such as induced inflammation, viral induced inflammation, and vascular grafts including surgery to the coronary side, angioplasty methods including angioplasty, stent insertion, endometrial resection, or arteries, veins, and capillaries It is useful for the treatment and prevention of inflammation associated with surgical methods such as other invasive methods including blood vessels. The present compounds are useful for the treatment of vascular-related diseases of the human body, but are not limited to these diseases. According to the present invention, the compound is administered to a subject in need of inhibition of angiogenesis. The method comprises neoplacia such as metastasis of affected area; Eye diseases such as retinal neovascular regeneration, including renal revascularization following injury or infection, diabetic retinopathy, macular degeneration, posterior capsular fibrosis, neovascular glaucoma; Ulcerative diseases such as gastric ulcer; Pathological, non-malignant diseases, including invantyl hemaginoma, angiofibroma of the nose, and nonvascular vasculature of bone; It is useful for the treatment of female genital diseases such as endometritis. Compounds of the present invention are gastrointestinal cancers such as colorectal cancer, brain cancer, bone cancer, basal cell carcinoma, epithelial cell-derived neoplasma (epithelial malignancy), adeno malignancy, lip cancer, mouth cancer, esophageal cancer, small intestine cancer and gastric cancer. To nourish skin cancer, prostate cancer, renal cell malignancy, and epithelial cells of the body, such as colon cancer, liver cancer, bladder cancer, pancreatic cancer, uterine cancer, cervical cancer, lung cancer, breast cancer and squamous cell carcinoma and basal cell carcinoma Useful for the treatment and prevention of other known cancers. Preferably, neoplacia is selected from gastrointestinal cancer, liver cancer, bladder cancer, pancreatic cancer, uterine cancer, prostate cancer, cervical cancer, lung cancer, breast cancer and skin cancers such as squamous cell cancer and basal cell cancer. It can also be used in the treatment of developing fibrosis. The method can be used for the treatment of subjects with athenomal polyps, such as familial adenoma polyposis (FAP). In addition, the method can also be used to prevent the formation of polyps in patients at risk of FAP. Administration of the compounds of the present invention may be used alone or in combination with additional therapies known to those skilled in the art for the treatment and prevention of neoplacia. Alternatively, the compounds described herein can be used in combination therapy. For example, the compound may be administered alone or in combination with other anticancer agents or other growth inhibitors or other drugs or nutritional agents. As there are a number of anticancer agents commercially available in clinical evaluation and incubation phase, they can be selected for treating Neoplacia by combination pharmaceutical chemotherapy. Such anticancer agents can be divided into several main categories, namely antibiotic type preparations, alkylating agents, metabolic antagonists, holmones, immunological agents, interferon type preparations, and other agents. Alternatively, other anticancer agents may be used, such as metal matrix proteases (MMPs), SOD mimetics, α v β 3 inhibitors. The first class of anticancer agents that can be used in combination with the compounds of the present invention consists of antiantagonist type anticancer agents. Suitable antiantagonist anticancer agents are 5-FU-fibrinogen, acanthiopolic acid, aminothiadiazole, brequina sodium, Carmofur, Ciba-Geigy CGP-30694, cyclopentyl cytosine, cytarabine phosphate stearate, cytarabine conjugate, Lilly DATHF, Merrel Dow DDFC, dezaquaanine, dideoxycytidine, dideoxyguano God, Dedox, Yoshitomi DMDC, Doxyfluidine, Wellcome EHNA, Merck & Co. EX-015, pazarabine, phloxuridine, fludarabine phosphate, 5-fluorouracil, N- (2'-furanidyl) -5-fluorouracil, Daiichi Seiyaku FO-152, isopropyl pyrrolidin , Lilly LY-188011, Lilly LY-264618, methotenzaprim, methotrexate, Wellcome MZPES, norpermidine, NCI NSC-127716, NCI NSC-264880, NCI NSC-39661, NCI NSC-612567, Warner-Lambert PALA, pento Statins, pyritreximes, plicamycins, Asahi Chemical PL-AC, Takeda TAC-788, thioguanine, thiazopurin, Erbamont TIF, trimetrexate, tyrosine kinase inhibitors, tyrosine protein kinase inhibitors, Taiho UFT and free lysine It is selected from the group consisting of tins. A second class of anticancer agents that can be used in combination with the compounds of the present invention consists of alkylated-type anticancer agents. Suitable alkylated-type anticancer agents include Shionogi 254-S, aldo-phosphamide analogs, altretamine, anoxiron, Boehringer Mannheim BBR-2207, Vestarabusil, Budo Titanium, Wakunaga CA-102, Carboplatin, Carmustine, Chinoin-139, Chinoin-153, Chlorambucil, Cisplatin, Cyclophosphamide, American Cyanamid CL-286558, Sanofi CY-233, Ciflatate, Degussa D-19-384, Sumimoto DACHP (Myr) 2, Diphenylspiromustine, Diplatinum Cytostatic, Erba Disamicin Derivatives, Chugai DWA-2114R, ITI E09, Elmustine, Erbamont FCE-24517, Estramustin Phosphate Sodium, Potemustine, Unimed G-6-M, Chinoin GYKI-17230, Hepsul-Farm, Iphosphamide, Iproplatin, Lomustine, Maposphamide, Mittol Lactol, Nippon Kayaku NK-121, NCI NSC-264395, NCI NSC-342215, Oxaliplatin, Upjohn PCNU, Red Nimustine, Proter PTT-119, Lanimustine, Semustine, SmithKline SK & F-101772, Yakult Honsha SN-22, Spyromus-Tin, Tanabe Seiyaku TA-077, Tauromustine, Temozolomide, Theoxiron, Tetra It is selected from the group consisting of platinum and trimella mole. A third class of anticancer agents that can be used in combination with the compounds of the present invention consists of antibiotic-type anticancer agents. Suitable antibiotic-type anticancer agents are Taiho 4181-A, aclarubicin, actinomycin D, actinoplanone. , Erbamont ADR-456, Aeroplysinine Derivatives, Ajinomoto AN-201-II, Ajinomoto AN-3, Nippon Soda Anisomycin, Anthracycline, Ajino-Mycin-A, Bisukaberine, Bristol-Myers BL-6859, Bristol-Myers BMY-25067, Bristol-Myers BMY-25551, Bristol-Myers BMY-26605, Bristol-Myers BMY-27557, Bristol-Myers BMY-28438, Bleomycin Sulfate, Briostatin-1, Taiho C-1027, Kalikemycin, Cromoximacin, Dactinomycin, Daunorubicin, Kyowa Hakko DC-102, Kyowa Hakko DC-79, Kyowa Hakko DC-88A, Kyowa Hakko DC89-A1, Kyowa Hakko DC92-B, Dietrisrubi Shin B, Shionogi DOB-41, doxorubicin, doxorubicin-fibrinogen, elsamicin-A, epirubicin, erbstatin, esorubicin, S Peramicin-A1, Esperamicin-A1b, Erbamont FCE-21954, Fujisawa FK-973, Postlysine, Fujisawa FR-900482, Glydobactin, Gregatin-A, Green Carmycin, Herbimycin, Idarubicin Shin, Illudins, Kazusamycin, Caesar Lordin, Kyowa Hakko KM-5539, Kirin Brewery KRN-8602, Kyowa Hakko KT-5432, Kyowa Hakko KT-5594, Kyowa Hakko KT-6149, American Cyanamid LL-D49194 , Meiji Seika ME 2303, menogaryl, mitomycin, mitoxantrone, SmithKline M-TAG, neoenactin, Nippon Kayaku NK-313, Nippon Kayaku NKT-01, SRI International NSC-357704, oxalicin, oxauomycin, Peptomycin, Pilate, Pirarubicin, Portramycin, Pyrindamycin A, Tobishi RA-I, Rapamycin, Lipocin, Rhodorubicin, Shivanomycin, Siwenmycin, Sumitomo SM-5887, Snow Brand SN- 706, Snow Brand SN-07, Solanzicin-A, Spasomycin, SS Pharmaceutical SS-21020, SS Pharmaceutical SS-7313B, SS Pharmaceutical SS-9816B, Stepymycin B, Taih o composed of 4181-2, thalisomycin, Takeda TAN-868A, terpenthecin, trazine, trichzarine A, Upjohn U-73975, Kyowa Hakko UCN-10028A, Fujisawa WF-3405, Yoshitomi Y-25024, and zorubicin Is selected from the group. A fourth class of anticancer agents that can be used in combination with the compounds of the invention is alpha-carotene, alpha-difluoromethyl-arginine, acitretin, Biotec AD-5, Kyorin AHC-52, alstonine, amonafide, amphetites Neil, Amsacrine, Angiostat, Ankinomycin, Anti-Neoplastone A10, Anti-Neoplastone A2, Anti-Neoplastone A3, Anti-Neoplastone A5, Antineoplasmon AS2-1, Henkel APD, Apidicholine glycinate, asparaginase, Avarol, baccarin, batracillin, benfluron, benzotript, Ipsen-Beaufour BIM-23015, bisantrene, Bristol-Myers BMY-40481, Vestar boron-10, Bromophosphamide, Welcome BW-502, Wellcome BW-773, Carracemide, Carmetizol Hydrochloride, Ajinomoto CDAF, Chlorsulfaquinoxalone, Chemes CHX-2053, Chemex CHX-100, Warner-Lambert CI-921, Warner-Lambert CI-937, Warner-Lambert CI-941, Warner-Lambert CI-958, clanfenur, clariridenone , ICN Compound 1259, ICN Compound 4711, Contracan, Yakult Honsha CPT-11, Crisnatol, Kuradum, Cytosalacin B, Cytarabine, Cytocithin, Merz D-609, DAbis Maleate, Dacazine, Datriptinium , Didenin-B, dihematopophyrin ether, dihydrorenferon, dynaline, distamycin, Toyo Pharmar DM-341, Toyo Pharmar DM-75, Daiichi Seiyaku DN-9693, eliprapin, elliptinium acetate, Tsumura EPMTC, Ergotamine, Etoposide, Etretinate, Penretinide, Fujisawa FR-57704, Gallium Nitrate, Genquadafnin, Chugai GLA-43, Glaxo GR-63178, Gripolan NMF-5N, Hexadecyl Phosphocholine, Green Cross HO-221, Homohartontonin, Hydroxyurea, BTG ICRF-187, Ilfofosin, Isoflutamine, Isotretinoin, Otsuka JI-36, Ramot K-477, Otsuak K-76COONa, Kureha Chemical K-AM, MECT Corp KI-8110, American Cyanamid L-623, Lukolegulin, Lonbeckamine, Lundbeck LU-23-112, Lilly LY-186641, NCI (US) MAP, Marie Sin, Merrel Dow MDL-27048, Medco MEDR-340, Merbaron, Merocyanine Derivatives, Methylanilinoacridine, Molecular Genetics MGI-136, Minatinibine, Mitonafide, Mitoquidone, Moridamole, Mortretinide , Zenyaku Kogyo MST-16, N- (retinoyl) amino acid, Nisshin Flour Milling N-021, N-acylated-dehydroalanine, napazathrom, Taisho NCU-190, nocodazole derivatives, Normosang, NCI NSC- 145813, NCI NSC-361456, NCI NSC-604782, NCI NSC-95580, Octreotide, Ono ONO-112, Oquizanosine, Akzo Org-10172, Pankrastatatin, Pazelliptin, Warner-Lambert PD-111707, Warner-Lambert PD-115934, Warner-Lambert PD-131141, Pierre Fabre PE-1001, ICRT Peptide D, Pyroxanthrone, Polyhematopophylline, Polypreic Acid, Efamol Porphyrin, Proviman, Procarbazine, Proglumid , Invitron Protease Nexin I, Tobishi RA-700, Lagyosan, Sapporo Breweries RBS, Lestritin-P, Retelliptin, Retinoic Acid, Rhone-Poulenc RP-49532, Rhone-Poulenc RP-56976, SmithKline SK & F-104864, Sumitomo SM-108, Kuraray SMANCS, SeaPharm SP-10094, Spartol, Spirocyclopropane derivatives, Spirogermanium, Unimed, SS Pharmaceutical SS-554, Stripoldinone, Stypoldione, Suntory SUN 0237, Suntory SUN 2071, Superoxide Dismutase, Toyama T-506, Toyama T-680, Taxol, Teijin TEI-0303, Teniposide, Tallyblastine, Eastman Kodak TJB-29, Tocotrienol, Topostin, Teijin TT Consists of -82, Kyowa Hakko UCN-01, Kyowa Hakko UCN-1028, Ukrain, Eastman Kodak USB-006, Vinetramide, Vinorelvine, Vintriptol, Vinzolidine, Witanolide, and Yamanouchi YM-534 do. Examples of radioprotective agents that can be used in combination with the compounds of the present invention include AD-5, adchnon, amifostine analogues, detox, dimesna, 1-102, MM-159, N-acylated- Dehydroalanine, TGF-Genentech, thiprotimod, amifostine, WR-151327, FUT-187, ketoprofen transdermal, nabumetone, superoxide dismutase (Chiron) and superoxide dismutase Enzon . In addition to being useful for the treatment of humans, these compounds are also useful for the treatment of livestock of pets, exotic animals and farm animals, including mammals, rodents and the like. More preferred animals include horses, dogs, and cats. The present invention may also be used in adjuvant therapy, in part or in place of conventional anti-inflammatory agents such as steroids, NSAIDs, iNOS inhibitors, 5-lipoxygenase inhibitors, LTB 4 receptor antagonists and LTA 4 hydrolase inhibitors. Suitable LTA 4 hydrolase inhibitors include PR-64966, (S, S) -3-amino-4- (4-benzyloxyphenyl) -2-hydroxybutyric acid benzyl ester (Scripps Res. Inst.), N- (2 (R)-(cyclohexylmethyl) -3- (hydroxycarbamoyl) propionyl) -L-alanine (Searle), 7- (4- (4-ureidobenzyl) phenylheptanoic acid (Rhone- Poulenc Rorer), and 3- (3- (1E, 3E-tetradecadienyl) -2-oxyranyl) benzoic acid lithium salt (Searle). Suitable LTB 4 receptor antagonists include, among others, axelen, linazolast, ontazolast, Bayer Bay-x-1005, Ciba Geigy compound CGS-25019C, Leo Denmark compound ETH-615, Merck compound MAFP, Terumo compound TMK- 688, Tanabe Compound T-0757, Lilly Compound LY-213024, LY-210073, LY-223982, LY233469, and LY255283, LY-293111, 264086 and 292728, ONO Compounds ON0-LB457, ON0-4057, and ONO-LB- 448, Shionogi Compound S-2474, Calcitral, Lilly Compound Searle Compound SC-53228, SC-41930, SC-50605 and SC-51146, Warner Lambert Compound BPC 15, SmithKline Beecham Compound SB-209247 and SK & F Compound SKF-104493 Include. Preferably, the LTB 4 receptor antagonist is calcitral, exelen, Bayer Bay-x-1005, Ciba Geigy compound CGS-25019C, Leo Denmark compound ETH-615, Lilly compound LY-293111, Ono compound ON0-4057, and Terumo compound TMK-688. Suitable 5-LO inhibitors include, among other compounds, Abbott compounds A-76745, 78773 and ABT761, Bayer Bay-x-1005, Cytomed CMI-392, Eisai E-3040, Scotia Pharmaceutica EF-40, Fujirebio F-1322, Merckle ML-3000, Purdue Frederick PF-5901, 3M Pharmaceuticals R-840, Lilopirox, Flubufen, Linasolast, Ronapollen, Mazoprocol, Ontazolast, Tenipap, Zylurton, Franlukast, Tepxaline , Lilopyrox, plezelastine hydrochloride, enazadrem phosphate, and bunaprolast. Compounds of the present invention may also be used in narcotic analgesics, Mu receptor antagonists, Kappa receptor antagonists, nonnarcotic (ie non-toxic) analgesics, monoamine uptake inhibitors, adenosine modulators, cannabinoid derivatives, Substance P antagonists, neurokinin-1 It can also be used in combination therapy with drugs and other analgesics, including receptor antagonists and sodium channel blockers. More preferably, mole pin, meperidine, codeine, pentazosin, buprenorphine, butorpanol, dezosin, meptazinol, hydrocodone, oxycodone, methadone, Tramadol [(+) enantiomer], DuP 747, Dynorphine A, Enadoline, RP-60180, HN-11608, E-2078, ICI-204448, acetominophene (paraceta mole), propoxyphene, nalbuphine, E-4018, filtenadol, mirfentanil, amitrip Tilin, DuP631, Tramadol [(-) enantiomer], GP-531, Acadecin, AKI-1, AKI-2, GP-1683, GP-3269, 4030W92, Tramadol Racemate, Dynorphine A, E-2078, Combination with a compound selected from AXC3742, SNX-111, ADL2-1294, ICI-204448, CT-3, CP-99, 994 and CP-99,994. It can be used in combination with one or more antihistamines, decongestants, diuretics, antitussives, and other agents known to be effective in combination with anti-inflammatory agents. The term "prevention" includes preventing the onset of clinically evident cardiovascular disease or preventing the onset of a latent evidence phase of cardiovascular disease for each individual. The phrase "therapeutically-effective" is intended to determine the amount of each compound to achieve the goal of improving the intensity and incidence of the disease while avoiding the typical side effects associated with alternative therapies. The present invention preferably includes compounds that selectively inhibit cyclooxygenase-2 over cyclooxygenase-1. Preferably, the compound has a cyclooxygenase-2 IC 50 of 0.5 μM or less, and the ratio of the selectivity of cyclooxygenase-2 to cyclooxygenase-1 is also at least 50, more preferably at least 100 to be. More preferably, the compound has a cyclooxygenase-1 IC 50 of about 5 μM or more. Such preferred selectivity exhibits the ability to reduce the incidence of conventional NSAID-induced side effects. Preferred classes of compounds are those wherein X in formula I is oxygen or sulfur; Wherein R is selected from carboxyl, lower alkyl, lower aralkyl and lower alkoxycarbonyl; R 1 is selected from lower haloalkyl, lower cycloalkyl and phenyl; R 2 is hydrido, halo, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, lower alkylamino, nitro, amino, aminosulfonyl, lower alkylaminosulfonyl, 5- or 6-membered heteroarylalkyl One or more radicals selected from aminosulfonyl, lower aralkylaminosulfonyl, 5- or 6-membered nitrogen-containing heterocyclosulfonyl, lower alkylsulfonyl, optionally substituted phenyl, lower aralkylcarbonyl, and lower alkylcarbonyl ego; R 2 consists of a compound of formula (I) or an isomer or a pharmacologically acceptable salt thereof which forms together with ring A a naphthyl radical. More preferred classes of compounds are those wherein X in formula I is oxygen or sulfur; R is carboxyl; R 1 is selected from lower haloalkyl; R 2 is hydrido, halo, lower alkyl, lower haloalkyl, lower haloalkoxy, lower alkylamino, amino, aminosulfonyl, lower alkylaminosulfonyl, 5- or 6-membered heteroarylalkylaminosulfonyl, lower A compound or isomer of formula (I) which is one or more radicals selected from aralkylaminosulfonyl, lower alkylsulfonyl, 6-membered nitrogen-containing heterocyclosulfonyl, optionally substituted phenyl, lower aralkylcarbonyl, and lower alkylcarbonyl Pharmacologically acceptable salts thereof. Even more preferred classes of compounds are those wherein R in formula I is carboxyl; R 1 is fluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluoroethyl, difluoromethyl, and trifluoromethyl; R 2 is hydrido, chloro, fluorine, bromo, iodo, methyl, ethyl, isopropyl, t-butyl, butyl, isobutyl, pentyl, hexyl, methoxy, ethoxy, isopropyloxy, tertbutyloxy , Trifluoromethyl, difluoromethyl, trifluoromethoxy, amino, N, N-dimethylamino, N, N-diethylamino, N-phenylmethylaminosulfonyl, N-phenylethylaminosulfonyl, N- ( 2-furylmethyl) aminosulfonyl, nitro, N, N-dimethylaminosulfonyl, aminosulfonyl, N-methylaminosulfonyl, N-ethylsulfonyl, 2,2-dimethylethylaminosulfonyl, N, N One selected from -dimethylaminosulfonyl, N- (2-methylpropyl) aminosulfonyl, N-morpholinosulfonyl, methylsulfonyl, benzylcarbonyl, 2,2-dimethylpropylcarbonyl, phenylacetyl, and phenyl Is a radical; R 2 consists of a compound of formula (I) or an isomer or a pharmacologically acceptable salt thereof which forms together with ring A a naphthyl radical. Even more preferred classes of compounds are those wherein R in formula I is carboxyl; R 1 is trifluoromethyl or pentafluoroethyl; And R2 is hydrido, chloro, fluorine, bromo, iodo, methyl, ethyl, isopropyl, t-butyl, methoxy, trifluoromethyl, trifluoromethoxy, N-phenylmethylaminosulfonyl, N- Phenylethylaminosulfonyl, N-methylaminosulfonyl, N- (2,2-dimethylethyl) aminosulfonyl, dimethylaminosulfonyl, 2-methylpropylaminosulfonyl, N-morpholinosulfonyl, methylsulfonyl , Benzylcarbonyl, and phenyl; R 2 consists of a compound of formula (I) or an isomer or a pharmacologically acceptable salt thereof which forms together with ring A a naphthyl radical. Preferred classes of compounds include those in formula I 'wherein X is O, S, CR c R b and NR a ; R a is hydrido, C 1 -C 3 -alkyl, (optionally substituted phenyl) -C 1 -C 3 -alkyl, acyl and carboxy-C 1 -C 6 -alkyl; R b and R b are each hydrido, C 1 -C 3 -alkyl, phenyl-C 1 -C 3 -alkyl, C 1 -C 3 -perfluoroalkyl, chloro, C 1 -C 6 -alkylthio, Independently selected from C 1 -C 6 -alkoxy, nitro, cyano and cyano-C 1 -C 3 -alkyl; R is selected from carboxyl, aminocarbonyl, C 1 -C 6 -alkylsulfonylaminocarbonyl and C 1 -C 6 -alkoxycarbonyl; R 'is selected from hydrido, phenyl, thienyl and C 2 -C 6 -alkenyl; R 1 is selected from C 1 -C 3 -perfluoroalkyl, chloro, C 1 -C 6 -alkylthio, C 1 -C 6 -alkoxy, nitro, cyano and cyano-C 1 -C 3 -alkyl ; R 2 is hydrido, halo, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, halo-C 2 -C 6 -alkynyl, aryl-C 1 -C 3 -alkyl, aryl-C 2 -C 6 -alkynyl, aryl-C 2 -C 6 -alkynyl, C 1 -C 6 -alkoxy, methylenedioxy, C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfinyl, aryloxy, arylthio, arylsulfinyl, heteroaryloxy, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkoxy, hetero Aryl-C 1 -C 6 -alkyloxy, aryl-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -haloalkoxy, C 1- C 6 -haloalkylthio, C 1 -C 6 -haloalkylsulfinyl, C 1 -C 6 -haloalkylsulfonyl, C 1 -C 3- (haloalkyl-C 1 -C 3 -hydroxyalkyl, C 1- C 6 -hydroxyalkyl, hydroxyamino-C 1 -C 6 -alkyl, C 1 -C 6 -alkylamino, arylamino, aryl-C 1 -C 6 -alkylamino, heteroarylamino, heteroaryl -C 1 -C 6 -alkylamino, nitro, cyano, amino, aminosulfonyl, C 1 -C 6- Alkylaminosulfonyl, arylaminosulfonyl, heteroarylaminosulfonyl, aryl-C 1 -C 6 -alkylaminosulfonyl, heteroaryl-C 1 -C 6 -alkylaminosulfonyl, heterocyclylsulfonyl, C 1 -C 6 -alkylsulfonyl, aryl-C 1 -C 6 -alkylsulfonyl, optionally substituted aryl, optionally substituted heteroaryl, aryl-C 1 -C 6 -alkylcarbonyl, heteroaryl-C 1 -C 6 -alkylcarbonyl, heteroarylcarbonyl, arylcarbonyl, aminocarbonyl, C 1 -C 6 -alkoxycarbonyl, formyl, C 1 -C 6 -haloalkylcarbonyl and C 1 -C 6 -alkylcarbon At least one radical selected from carbonyl; A ring atoms A 1 , A 2 , A 3 , and A 4 are carbon and nitrogen provided that at least three of A 1 , A 2 , A 3 , and A 4 are carbon; Independently selected from; Or R 2 consists of a compound of formula (I ′) or an isomer or a pharmacologically acceptable salt thereof which forms together with ring A a naphthyl or quinolyl radical. More preferred class of compounds is that X in Formula I 'is selected from O, S, and NR a ; R a is selected from hydrido, C 1 -C 3 -alkyl and (optionally substituted phenyl) methyl; R 'is selected from hydrido and C 2 -C 6 -alkenyl; R is carboxyl; R 1 is selected from C 1 -C 3 -perfluoroalkyl; R 2 is hydrido, halo, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, halo-C 2 -C 6 -alkynyl, phenyl-C 1 -C 6 -alkyl, phenyl-C 2 -C 6 -alkynyl, phenyl-C 2 -C 6 -alkenyl, C 1 -C 3 -alkoxy, methylenedioxy, C 1 -C 3 -alkoxy-C 1 -C 3 -alkyl, C 1 -C 3 -alkylthio, C 1 -C 3 -alkylsulfinyl, phenyloxy, phenylthio, phenylsulfinyl, C 1 -C 3 -haloalkyl-C 1 -C 3- Hydroxyalkyl, phenyl-C 1 -C 3 -alkyloxy-C 1 -C 3 -alkyl, C 1 -C 3 -haloalkyl, C 1 -C 3 -haloalkoxy, C 1 -C 3 -haloalkylthio , C 1 -C 3 -hydroxyalkyl, C 1 -C 3 -alkoxy-C 1 -C 3 -alkyl, hydroxyamino-C 1 -C 3 -alkyl, C 1 -C 6 -alkylamino, nitro, Cyano, amino, aminosulfonyl, N-alkylaminosulfonyl, N-arylaminosulfonyl, N-heteroarylaminosulfonyl, N- (phenyl-C 1 -C 6 -alkyl) aminosulfonyl, N- (heteroaryl, -C 1 -C 6 - alkyl) aminosulfonyl, phenyl -C 1 -C 3 - alkylsulfonyl, 5- to 8-membered Interrogating cycle ilsul sulfonyl, C 1 -C 6 - alkylsulfonyl, optionally substituted phenyl, optionally substituted 5- to 9-membered heteroaryl, phenyl -C 1 -C 6 - alkyl-carbonyl, phenyl-carbonyl, 4- One independently selected from chlorophenylcarbonyl, 4-hydroxyphenylcarbonyl, 4-trifluoromethylphenylcarbonyl, 4-methoxyphenylcarbonyl, aminocarbonyl, formyl, and C 1 -C 6 -alkylcarbonyl Is a radical; A ring atoms A 1 , A 2 , A 3 and A 4 are independently selected from carbon and nitrogen provided that at least three of A 1 , A 2 , A 3 and A 4 are carbon; R 2 consists of a compound of formula (I ′) or an isomer or a pharmacologically acceptable salt thereof that forms together with ring A a naphthyl, benzofurylphenyl or quinolyl radical. A more preferred class of compounds is that X in Formula I 'is selected from O, S and NR a ; R a is hydrido, methyl, ethyl, (4-trifluoromethyl) benzyl, (4-chloromethyl) benzyl, (4-methoxy) benzyl, and (4-cyano) benzyl, (4-nitro) Benzyl; R is carboxyl; R 'is selected from hydrido and ethenyl; R 1 is selected from trifluoromethyl and pentafluoroethyl; R 2 is hydrido, chloro, bromo, fluorine, iodo, methyl, t-butyl, ethenyl, ethynyl, 5-chloro-1-pentynyl, 1-pentynyl, 3,3-dimethyl-1 -Butynyl, benzyl, phenylethyl, phenyl-ethynyl, 4-chlorophenyl-ethynyl, 4-methoxyphenyl-ethynyl, phenylethenyl, methoxy, methylthio, methylsulfinyl, phenyloxy, phenylthio , Phenylsulfinyl, methylenedioxy, benzyloxymethyl, trifluoromethyl, difluoromethyl, pentafluoroethyl, trifluoromethoxy, trifluoromethylthio, hydroxymethyl, hydroxy-trifluoroethyl, methoxymethyl, Hydroxyiminomethyl, N-methylamino, nitro, cyano, amino, aminosulfonyl, N-methylaminosulfonyl, N-phenylaminosulfonyl, N-furylaminosulfonyl, N- (benzyl) aminosulfonyl , N- (furylmethyl) aminosulfonyl, benzylsulfonyl, phenylethylaminosulfonyl, furylsulfonyl, methylsulfonyl, phenyl, chloro, fluorine , Phenyl, benzimidazolyl, thienyl, chloro, furyl, chloro-substituted furyl, benzylcarbonyl, optionally substituted phenylcarbonyl substituted with one or more radicals selected from bromo, methoxy, methylthio and methylsulfonyl At least one radical independently selected from thienyl substituted with aminocarbonyl, formyl and methylcarbonyl; A ring atoms A 1 , A 2 , A 3 and A 4 are selected from carbon and nitrogen provided that at least three of A 1 , A 2 , A 3 and A 4 are carbon; R 2 consists of a compound of formula (I ′) or an isomer or a pharmacologically acceptable salt thereof which forms together with ring A a naphthyl or quinolyl radical. Within formula I ', X is O; R is carboxyl; R '' is selected from hydrido and C 2 -C 6 -alkenyl; R 1 is selected from C 1 -C 3 -perfluoroalkyl; R 2 is hydrido, halo, C 1 -C 6 -alkyl, phenyl-C 1 -C 6 -alkyl, phenyl-C 2 -C 6 -alkynyl, phenyl-C 2 -C 6 -alkenyl, C 1- C 6 -alkoxy, phenyloxy, 5- or 6-membered heteroaryloxy, phenyl-C 1 -C 6 -alkyloxy, 5- or 6-membered heteroaryl-C 1 -C 6 -alkyloxy, C 1- C 6 -haloalkyl, C 1 -C 6 -haloalkoxy, N- (C 1 -C 6 -alkyl) amino, N, N-di- (C 1 -C 6 -alkyl) amino, N-phenyl Amino, N- (phenyl-C 1 -C 6 -alkyl) amino, N-heteroarylamino, N- (heteroaryl-C 1 -C 6 -alkyl) amino, nitro, amino, aminosulfonyl, N- ( C 1 -C 6 -alkyl) aminosulfonyl, N, N-di- (C 1 -C 6 -alkyl) aminosulfonyl, N-arylaminosulfonyl, N-heteroarylaminosulfonyl, N- (phenyl -C 1 -C 6 - alkyl) aminosulfonyl, N- (heteroaryl, -C 1 -C 6 - alkyl) aminosulfonyl, 5- to 8-membered heterocyclic ilsul sulfonyl, C 1 -C 6 - alkyl alcohol Ponyl, optionally substituted phenyl, optionally substituted 5- or 6-membered heteroaryl, phenyl- C 1 -C 6 - alkyl-carbonyl, heteroaryl-carbonyl, phenyl-carbonyl, aminocarbonyl, and C 1 -C 6 - alkyl, and independently one or more radicals selected from carbonyl; A ring atoms A 1 , A 2 , A 3 and A 4 are selected from carbon and nitrogen, or isomers or pharmacologically acceptable, provided that at least three of A 1 , A 2 , A 3 and A 4 are carbon Possible salts thereof. More preferred classes of compounds include those in Formula I 'wherein X is O; R is carboxyl; R '' is selected from hydrido and ethenyl; R 1 is selected from trifluoromethyl and pentafluoroethyl; R 2 is hydrido, chloro, bromo, fluorine, iodo, methyl, t-butyl, ethenyl, ethynyl, 5-chloro-1-pentynyl, 1-pentynyl, 3,3-dimethyl-1 -Butynyl, benzyl, phenylethyl, phenyl-ethynyl, 4-chlorophenyl-ethynyl, 4-methoxyphenyl-ethynyl, phenylethenyl, methoxy, methylthio, methylsulfinyl, phenyloxy, phenylthio , Phenylsulfinyl, pyridyloxy, thienyloxy, furyloxy, phenylmethoxy, methylenedioxy, benzyloxymethyl, trifluoromethyl, difluoromethyl, pentafluoroethyl, trifluoromethoxy, trifluoromethylthio, Hydroxymethyl, hydroxy-trifluoroethyl, methoxymethyl, hydroxyiminomethyl, N-methylamino, N-phenylamino, N- (benzyl) amino, nitro, cyano, amino, aminosulfonyl, N- Methylaminosulfonyl, N-phenylaminosulfonyl, N-furylaminosulfonyl, N- (benzyl) aminosulfonyl, N- (furylmethyl) aminosulfonyl, benzyl Phenyl, benzimidazolyl, thienyl substituted with one or more radicals selected from phenyl, phenylethylaminosulfonyl, furylsulfonyl, methylsulfonyl, phenyl, chloro, fluorine, bromo, methoxy, methylthio and methylsulfonyl At least one radical independently selected from chloro, furyl, chloro, benzylcarbonyl, furylcarbonyl, phenylcarbonyl, aminocarbonyl, formyl, and thienyl substituted with phenylcarbonyl; One of the A ring atoms A 1 , A 2 , A 3 , and A 4 is nitrogen, and the other three are carbon compounds or isomers or pharmacologically acceptable salts thereof. Another more preferred class of compounds is X is O; R is carboxyl; R '' is selected from hydrido and ethenyl; R 1 is selected from trifluoromethyl and pentafluoroethyl; R 2 is hydrido, chloro, bromo, fluorine, iodo, methyl, t-butyl, ethenyl, ethynyl, 5-chloro-1-pentynyl, 1-pentynyl, 3,3, -dimethyl- 1-butynyl, benzyl, phenylethyl, phenyl-ethynyl, 4-chlorophenyl-ethynyl, 4-methoxyphenyl-ethynyl, phenylethenyl, methoxy, methylthio, methylsulfinyl, phenyloxy, phenyl Thio, phenylsulfinyl, pyridyloxy, thienyloxy, furyloxy, phenylmethoxy, methylenedioxy, benzyloxymethyl, trifluoromethyl, difluoromethyl, pentafluoroethyl, trifluoromethoxy, trifluoromethylthio , Hydroxymethyl, hydroxy-trifluoroethyl, methoxymethyl, hydroxyaminomethyl, N-methylamino, N-phenylamino, N- (benzyl) amino, nitro, cyano, amino, aminosulfonyl, N -Methylaminosulfonyl, N-phenylaminosulfonyl, N-furylaminosulfonyl, N- (benzyl) aminosulfonyl, N- (furylmethyl) aminosulfonyl, benzyl Phenyl, benzimidazolyl, tier substituted with one or more radicals selected from sulfonyl, phenylethylaminosulfonyl, furylsulfonyl, methylsulfonyl, phenyl, chloro, fluorine, bromo, methoxy, methylthio and methylsulfonyl At least one radical independently selected from niyl, chloro, furyl, chloro, benzylcarbonyl, furylcarbonyl, phenylcarbonyl, aminocarbonyl, formyl, and thienyl substituted with methylcarbonyl; A ring atoms A 1 , A 2 , A 3 , and A 4 consist of a compound of formula (I ′) or an isomer or pharmacologically acceptable salt thereof that is carbon. In formula (I ') X is S; R is carboxyl; R 1 is selected from C 1 -C 3 -perfluoroalkyl; R 2 is hydrido, halo, C 1 -C 6 -alkyl, phenyl-C 1 -C 6 -alkyl, phenyl-C 2 -C 6 -alkynyl, phenyl-C 2 -C 6 -alkenyl, C 1- C 6 -alkoxy, phenyloxy, 5- or 6-membered heteroaryloxy, phenyl-C 1 -C 6 -alkoxy, 5- or 6-membered heteroaryl-C 1 -C 6 -alkyloxy, C 1 -C 6 -haloalkyl, C 1 -C 6 -haloalkoxy, C 1 -C 6 -alkylamino, N-phenylamino, N- (phenyl-C 1 -C 6 -alkyl) amino, N-heteroarylamino , N- (heteroaryl) -C 1 -C 6 -alkylamino, nitro, amino, aminosulfonyl, N-alkylaminosulfonyl, N-arylaminosulfonyl, N-heteroarylaminosulfonyl, N- ( Phenyl-C 1 -C 6 -alkyl) aminosulfonyl, N- (heteroaryl-C 1 -C 6 -alkyl) aminosulfonyl, 5- to 8-membered heterocyclylsulfonyl, C 1 -C 6 -alkyl Sulfonyl, optionally substituted phenyl, optionally substituted 5- or 6-membered heteroaryl, phenyl-C 1 -C 6 -alkylcarbonyl, heteroarylcarbonyl, phenylcarbonyl, aminocarbonyl, And one or more radicals independently selected from C 1 -C 6 -alkylcarbonyl; A ring atoms A 1 , A 2 , A 3 , and A 4 are independently selected from oxygen and nitrogen provided that at least three of A 1 , A 2 , A 3 , and A 4 are carbon; There is another subclass that is a pyran compound or an isomer thereof or a pharmacologically acceptable salt thereof. More preferred classes of compounds include those in Formula I 'wherein X is S; R is carboxyl; R '' is selected from hydrido and ethenyl; R 1 is selected from trifluoromethyl and pentafluoroethyl; R 2 is hydrido, chloro, bromo, fluorine, iodo, methyl, t-butyl, ethenyl, ethynyl, 5-chloro-1-pentynyl, 1-pentynyl, 3,3-dimethyl-1 -Butynyl, benzyl, phenylethyl, phenyl-ethynyl, phenylethenyl, methoxy, methylthio, methylsulfinyl, phenyloxy, phenylthio, phenylsulfinyl, pyridyloxy, thienyloxy, furyloxy, phenyl Methoxy, methylenedioxy, benzyloxymethyl, trifluoromethyl, difluoromethyl, pentafluoroethyl, trifluoromethoxy, trifluoromethylthio, hydroxymethyl, hydroxy-trifluoroethyl, methoxymethyl, hydroxyyi Minomethyl, N-methylamino, N-phenylamino, N- (benzyl) amino, nitro, cyano, amino, aminosulfonyl, N-methylaminosulfonyl, N-phenylaminosulfonyl, N-furylaminosul Phonyl, N- (benzyl) aminosulfonyl, N- (furylmethyl) aminosulfonyl, benzylsulfonyl, phenyletherylaminosulfonyl, furylsulfonyl, Phenyl, benzimidazolyl, thienyl, chloro, furyl, chloro, benzylcarbonyl, furyl substituted with one or more radicals selected from methylsulfonyl, phenyl, chloro, fluorine, bromo, methoxy, methylthio and methylsulfonyl At least one radical independently selected from carbonyl, phenylcarbonyl, aminocarbonyl, formyl, and thienyl substituted with methylcarbonyl; A ring atoms A 1 , A 2 , A 3 , and A 4 are composed of a compound of formula (I ′) or an isomer thereof or a pharmacologically acceptable salt thereof which is carbon. In formula (I ') X is NR a ; R a is selected from hydrido, C 1 -C 3 -alkyl, phenyl-C 1 -C 3 -alkyl, acyl and carboxy-C 1 -C 3 -alkyl; R is carboxyl; R 1 is selected from C 1 -C 3 -perfluoroalkyl; R 2 is hydrido, halo, C 1 -C 6 -alkyl, phenyl-C 1 -C 6 -alkyl, phenyl-C 2 -C 6 -alkynyl, phenyl-C 2 -C 6 -alkenyl, C 1- C 6 -alkoxy, phenyloxy, 5- or 6-membered heteroaryloxy, phenyl-C 1 -C 6 -alkyloxy, 5- or 6-membered heteroaryl-C 1 -C 6 -alkyloxy, C 1- C 6 -haloalkyl, C 1 -C 6 -haloalkoxy, C 1 -C 6 -alkylamino, N-phenylamino, N- (phenyl-C 1 -C 6 -alkyl) amino, N-heteroaryl Amino, N- (heteroaryl) -C 1 -C 6 -alkylamino, nitro, amino, aminosulfonyl, N-alkylaminosulfonyl, N-arylaminosulfonyl, N-heteroarylaminosulfonyl, N- (Phenyl-C 1 -C 6 -alkyl) aminosulfonyl, N- (heteroaryl-C 1 -C 6 -alkyl) aminosulfonyl, 5- to 8-membered heterocyclylsulfonyl, C 1 -C 6- alkylsulfonyl, optionally substituted phenyl, optionally substituted 5- or 6-membered heteroaryl, phenyl -C 1 -C 6 - alkyl-carbonyl, heteroaryl-carbonyl, phenyl-carbonyl, amino-carbonyl And C 1 -C 6 - alkyl, and independently one or more radicals selected from carbonyl; A ring atoms A 1 , A 2 , A 3, and A 4 are dihydroquinoline compounds selected from carbon and nitrogen, provided that at least three of A 1 , A 2 , A 3, and A 4 are carbon; There is a third subclass, either an isomer or a pharmacologically acceptable salt thereof. More preferred classes of compounds are those wherein X is NR a ; R a is hydrido, methyl, ethyl, (4-trifluoromethyl) benzyl, (4-chloromethyl) benzyl, (4-methoxy) benzyl, (4-cyano) benzyl, and (4-nitro) Benzyl; R is carboxyl; R ″ is selected from hydrido, ethenyl; R 1 is selected from trifluoromethyl and pentafluoroethyl; R 2 is hydrido, chloro, bromo, fluorine, iodo, methyl, t-butyl, Ethenyl, ethynyl, 5-chloro-1-pentynyl, 1-pentynyl, 3,3-dimethyl-1-butynyl, benzyl, phenylethyl, phenyl-ethynyl, 4-chlorophenyl-ethynyl, 4 -Methoxyphenyl-ethynyl, phenylethenyl, methoxy, methylthio, methylsulfinyl, phenyloxy, phenylthio, phenylsulfinyl, pyridyloxy, thienyloxy, furyloxy, phenylmethoxy, methylenedioxy , Benzyloxymethyl, trifluoromethyl, difluoromethyl, pentafluoroethyl, trifluoromethoxy, trifluoromethylthio, hydroxymethyl, hydroxy-trifluoroethyl, methoxymethyl, hydroxyaminomethyl, N-methyl Amino, N-phenylamino, N- (benzyl) amino, nitro, cyano, amino, aminosulfonyl, N-methylamino Ponyl, N-phenylaminosulfonyl, N-furylaminosulfonyl, N- (benzyl) aminosulfonyl, N- (furylmethyl) aminosulfonyl, furylsulfonyl, methylsulfonyl, phenyl, chloro, fluorine, bro Phenyl, benzimidazolyl, thienyl, chloro, furyl, chloro, benzylcarbonyl, furylcarbonyl, phenylcarbonyl, aminocarbonyl, substituted with one or more radicals selected from parent, methoxy, methylthio and methylsulfonyl, Is one or more radicals independently selected from formyl, and thienyl substituted with methylcarbonyl; and the A ring atoms A 1 , A 2 , A 3 , and A 4 are carbon, or isomers or pharmacologically Acceptable salts thereof. In formula (I ') X is selected from O, S, and NR a ; R a is selected from hydrido, C 1 -C 3 -alkyl, phenyl-C 1 -C 3 -alkyl, acyl and carboxy-C 1 -C 3 -alkyl; R is carboxyl; R 1 is selected from C 1 -C 3 -perfluoroalkyl; A ring atoms A 1 , A 2 , A 3 and A 4 are selected from carbon and nitrogen provided that at least three of A 1 , A 2 , A 3 and A 4 are carbon; R 2 together with ring A has a fourth subclass which is naphthyl, or a compound which forms a quinolyl radical or an isomer thereof or a pharmacologically acceptable salt thereof. A more preferred class of compounds is that X in Formula I 'is selected from O, S, and NR a ; R a is hydrido, methyl, ethyl, (4-trifluoromethyl) benzyl, (4-chloromethyl) benzyl, (4-methoxy) benzyl, (4-cyano) benzyl, and (4-nitro) Benzyl; R is carboxyl; R 1 is selected from trifluoromethyl and pentafluoroethyl; A ring atoms A 1 , A 2 , A 3 , and A 4 are carbon; R 2 is composed of a compound of formula (I ′) or an isomer thereof or a pharmacologically acceptable salt thereof which forms together with ring A a naphthyl, or quinolyl radical. Within Formula I there is a subclassification of the very interesting compounds represented by Formula II or their isomers or pharmacologically acceptable salts thereof: Wherein X is selected from O, S, and NR a ; R 2 is lower haloalkyl; R 3 is selected from hydrido, and halo; R 4 is hydrido, halo, lower alkyl, lower haloalkoxy, lower alkoxy, lower aralkylcarbonyl, lower dialkylaminosulfonyl, lower alkylaminosulfonyl, lower aralkylaminosulfonyl, lower heteroaralkylamino Sulfonyl and 5- or 6-membered nitrogen containing heterocyclosulfonyl; R 5 is selected from hydrido, lower alkyl, halo, lower alkoxy, and aryl; And R 6 is selected from hydrido, halo, lower alkyl, lower alkoxy, and aryl. Of particular interest are classes of compounds wherein R 2 in formula II is trifluoromethyl or pentafluoroethyl; R 3 is selected from hydrido, chloro, and fluorine; R 4 is hydrido, chloro, bromo, fluorine, iodo, methyl, t-butyl, trifluoromethoxy, methoxy, benzylcarbonyl, dimethylaminosulfonyl, isopropylaminosulfonyl, methylaminosulfonyl Benzylaminosulfonyl, phenylethylaminosulfonyl, methylpropylaminosulfonyl, methylsulfonyl, and morpholinosulfonyl; R 5 is selected from hydrido, methyl, ethyl, isopropyl, t-butyl, chloro, methoxy, diethylamino, and phenyl; And R 6 consists of a compound of formula (II) selected from hydrido, chloro, bromo, fluorine, methyl, ethyl, t-butyl, methoxy, and phenyl or an isomer or pharmacologically acceptable salt thereof. Within Formula I there is a subclassification of the very interesting compounds represented by Formula IIa or their isomers or pharmacologically acceptable salts thereof: Wherein R 3 is selected from hydrido, lower alkyl, lower hydrooxyalkyl, lower alkoxy and haloboter; Wherein R 4 is hydrido, halo, lower alkyl, lower alkylthio, lower haloalkyl, amino, aminosulfonyl, lower alkylsulfonyl, lower alkylsulfinyl, lower alkoxyalkyl, lower alkylcarbonyl, formyl, cyano , Lower haloalkylthio, substituted or unsubstituted phenylcarbonyl, lower haloalkoxy, lower alkoxy, lower aralkylcarbonyl, lower dialkylaminosulfonyl, lower alkylaminosulfonyl, lower aralkylaminosulfonyl, lower hetero Aralkylaminosulfonyl, 5- or 6-membered heteroaryl, lower hydrooxyalkyl, optionally substituted phenyl and 5- or 6-membered nitrogen containing heterocyclosulfonyl; R 5 is selected from hydrido, lower alkyl, halo, lower haloalkyl, lower alkoxy, and phenyl; And R 6 is selected from hydrido, halo, cyano, hydrooxyiminomethyl, lower hydroxyalkyl, lower alkynyl, phenylalkynyl, lower alkyl, lower alkoxy, formyl and phenyl. Of particular interest are the classes of compounds wherein R 3 in formula (IIa) is selected from hydrido and chloro; R 4 is chloro, methyl, t-butyl, methylthio, trifluoromethyl, difluoromethyl, pentafluoromethyl, trifluoromethylsulfide, trifluoromethooxy, cyano, substituted or unsubstituted phenylcarbonyl, and Selected from substituted or unsubstituted phenyl; And R 5 is selected from hydrido, methyl, t-butyl, chloro; R 6 is a compound of Formula IIa or an isomer or pharmacologically acceptable salt thereof that is hydrido, chloro, thienyl, hydroxyiminomethyl, substituted or unsubstituted phenylethynyl, and substituted or unsubstituted phenyl It is composed. Within Formula I are subclassifications of the compounds of great interest represented by Formula IIb or their isomers or pharmacologically acceptable salts thereof: Wherein R 3 is selected from hydrido, lower alkyl, lower hydroxyalkyl, lower alkoxy and halo; R 4 is hydrido, halo, lower alkyl, lower alkylthio, lower haloalkyl, amino, aminosulfonyl, lower alkylsulfonyl, lower alkylsulfinyl, lower alkoxyalkyl, lower alkylcarbonyl, formyl, cyano, Lower haloalkylthio, substituted or unsubstituted phenylcarbonyl, lower haloalkoxy, lower alkoxy, lower aralkylcarbonyl, lower dialkylaminosulfonyl, lower alkylaminosulfonyl, lower aralkylaminosulfonyl, lower hetero Aralkylaminosulfonyl, 5- or 6-membered heteroaryl, lower hydrooxyalkyl, optionally substituted phenyl and nitrogen-containing heterocyclosulfonyl that is 5- or 6-membered; R 5 is selected from hydrido, lower alkyl, halo, lower haloalkyl, lower alkoxy, and phenyl; And R 6 is hydrido, halo, cyano, hydrooxyiminomethyl, lower hydroxyalkyl, lower alkynyl, phenylalkynyl, lower alkyl, lower alkoxy, formyl and phenyl; And or its isomers or pharmacologically acceptable salts thereof. Of particular interest are the classes of compounds wherein R 3 in formula (IIb) is selected from hydrido and chloro; R 4 is chloro, methyl, t-butyl, methylthio, trifluoromethyl, difluoromethyl, pentafluoromethyl, trifluoromethylsulfide, trifluoromethoxy, cyano, substituted or unsubstituted phenylcarbonyl, and substituted Selected from unsubstituted or substituted phenyl; And R 5 is selected from hydrido, methyl, t-butyl, chloro; R 6 is a compound of Formula IIb or an isomer or pharmacologically acceptable salt thereof that is hydrido, chloro, thienyl, hydroxyiminomethyl, substituted or unsubstituted phenylethynyl, and substituted or unsubstituted phenyl It is composed. Within Formula I there is a subclass of compounds of very high interest represented by Formula IIc: Wherein R a is selected from hydrido and lower aralkyl; R 3 is selected from hydrido, lower alkyl, lower hydroxyalkyl, lower alkoxy and halo; R 4 is hydrido, halo, lower alkyl, lower alkylthio, lower haloalkyl, amino, aminosulfonyl, lower alkylsulfonyl, lower alkylsulfinyl, lower alkoxyalkyl, lower alkylcarbonyl, formyl, cyano, Lower haloalkylthio, substituted or unsubstituted phenylcarbonyl, lower haloalkoxy, lower alkoxy, lower aralkylcarbonyl, lower dialkylaminosulfonyl, lower alkylaminosulfonyl, lower aralkylaminosulfonyl, lower hetero Aralkylaminosulfonyl, 5- or 6-membered heteroaryl, lower hydrooxyalkyl, optionally substituted phenyl and 5- or 6-membered nitrogen containing heterocyclosulfonyl; R 5 is selected from hydrido, lower alkyl, halo, lower haloalkyl, lower alkoxy, and phenyl; R 6 is hydrido, halo, cyano, hydrooxyiminomethyl, lower hydroxyalkyl, lower alkynyl, phenylalkynyl, lower alkyl, lower alkoxy, formyl and phenyl; Or isomers thereof or pharmacologically acceptable salts thereof. Of particular interest are the classes of compounds wherein R 3 in formula (IIc) is selected from hydrido and chloro; R 4 is chloro, methyl, t-butyl, methylthio, trifluoromethyl, difluoromethyl, pentafluoromethyl, trifluoromethylsulfide, trifluoromethoxy, cyano, substituted or unsubstituted phenylcarbonyl, and substituted Selected from unsubstituted or substituted phenyl; And R 5 is selected from hydrido, methyl, t-butyl, chloro; R 6 is a compound of Formula IIc or an isomer or pharmacologically acceptable salt thereof that is hydrido, chloro, thienyl, hydroxyiminomethyl, substituted or unsubstituted phenylethynyl, and substituted or unsubstituted phenyl It is composed. Of particular interest within the compounds of formula (I) are the populations of the following compounds and their isomers or pharmacologically acceptable salts thereof: 6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 2,7-bis (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 7-bromo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-7-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8- (1-methylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-7- (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (1-methylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-ethoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7- (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-bromo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-bromo-6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-trifluoromethoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 5,7-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7,8-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7-isopropyloxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-phenyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7,8-dimethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-bis (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7- (1-methylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7-phenyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-7-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-7-phenyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,7-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-dibromo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-dimethoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-nitro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-amino-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; Ethyl 6-amino-2-trifluoromethyl-2H-1-benzopyran-3-carboxylate; 6-chloro-8-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-chloro-6-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-chloro-6-methoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-difluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-bromo-8-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-bromo-6-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-bromo-6-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-bromo-5-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-bromo-8-methoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7- (N, N-diethylamino) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[[(phenylmethyl) amino] sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[(dimethylamino) sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-aminosulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6- (methylamino) sulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[(4-morpholino) sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[(1,1-dimethylethyl) aminosulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[(2-methylpropyl) aminosulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-methylsulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-chloro-6-[[(phenylmethyl) amino] sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-N, N-diethylaminosulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-phenylacetyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6- (2,2-dimethylpropylcarbonyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-dichloro-7-methoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[[(furanylmenyl) amino] sulfonyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-[(phenylmethyl) sulfonyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-[[(phenylethyl) amino] sulfonyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-iodo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 8-bromo-6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-formyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-formyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-bromo-7- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 5,6-dichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-cyano-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-hydroxymethyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (difluoromethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 2,6-bis (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 5,6,7-trichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6,7,8-trichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (methylthio) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (methylsulfinyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 5,8-dichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (pentafluoroethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 2- (trifluoromethyl) -6-[(trifluoromethyl) thio] -2H-1-benzopyran-3-carboxylic acid; 6,8-dichloro-7-methyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-2,7-bis (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 5-methoxy-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-benzoyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (4-chlorobenzoyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (4-hydroxybenzoyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-phenoxy-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 8-chloro-6- (4-chlorophenoxy) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 2- (trifluoromethyl) -6- [4- (trifluoromethyl) phenoxy) -2H-1-benzopyran-3-carboxylic acid; 6- (4-methoxyphenoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (3-chloro-4-methoxyphenoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (4-chlorophenoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 8-chloro-2- (trifluoromethyl) -6- [4- (trifluoromethyl) phenoxy] -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-cyano-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-[(hydroxyimino) methyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (hydroxymethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 8- (1H-benzimidazol-2-yl) -6-chloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 7- (1,1-dimethylethyl) -2- (pentafluoroethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (methoxymethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (benzyloxymethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-ethenyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-ethynyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (2-thienyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (2-furanyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (5-chloro-1-pentynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (1-pentynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (phenylethynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (3,3-dimethyl-1-butynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-[(4-chlorophenyl) ethynyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-[(4-methoxyphenyl) ethynyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (phenylethynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (4-chlorophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (3-methoxyphenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-[(4-methylthio) phenyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-[(4-methylsulfonyl) phenyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-phenyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-bromo-8-fluoro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (4-fluorophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-phenyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 8-chloro-6-fluoro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6,8-diiodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (5-chloro-2-thienyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (2-thienyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (4-chlorophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (4-bromophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (ethynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-methyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (4-methoxyphenyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-2- (trifluoromethyl) -4-ethenyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-2- (trifluoromethyl) -4-phenyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-4- (2-thienyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (2,2,2-trifluoro-1-hydroxyethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 6,8-dimethyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 6- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 7-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 6,7-dimethyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 8-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 6-chloro-7-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 7-chloro-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 6,7-dichloro-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 2- (trifluoromethyl) -6-[(trifluoromethyl) thio] -2H-1-benzothiopyran-3-carboxylic acid; 6,8-dichloro-2-trifluoromethyl-2H-1-benzothiopyran-3-carboxylic acid; 6-chloro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6,8-dichloro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6,7-difluoro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-iodo-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-bromo-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 1,2-dihydro-6- (trifluoromethoxy) -2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6- (trifluoromethyl) -1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-cyano-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-chloro-1,2-dihydro-1-methyl-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-chloro-1,2-dihydro-2- (trifluoromethyl) -1-[[4- (trifluoromethyl) phenyl] methyl] -3-quinolinecarboxylic acid; 6-chloro-1-[(4-chlorophenyl) methyl] -1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-chloro-1,2-dihydro-2- (trifluoromethyl) -1-[[4- (methoxy) phenyl] methyl] -3-quinolinecarboxylic acid; 6-chloro-1-[(4-cyanophenyl) methyl] -1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-chloro-1,2-dihydro-1-[(4-nitrophenyl) methyl] -2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-chloro-1,2-dihydro-1-ethyl-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-chloro-2- (trifluoromethyl) -1,2-dihydro [1,8] naphthyridine-3-carboxylic acid; 2-trifluoromethyl-2H-naphtho [1,2-b] pyran-3-carboxylic acid; 2-trifluoromethyl-3H-naphtho [2,1-b] pyran-3-carboxylic acid; 2-trifluoromethyl-2H-naphtho [2,3-b] pyran-3-carboxylic acid; 5- (hydroxymethyl) -8-methyl-2- (trifluoromethyl) -2H-pyrano [2,3-c] pyridine-3-carboxylic acid; 6- (trifluoromethyl) -6h-1,3-dioxolo [4,5-g] [1] benzopyran-7-carboxylic acid; And 3- (trifluoromethyl) -3H-benzofuro [3,2-f] [1] benzopyran-2-carboxylic acid. A group of compounds of particular interest within the range of formulas I and I 'consist of the following compounds and their pharmacologically acceptable salts: (S) -6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -7-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -7-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -2,7-bis (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -7-bromo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-7-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -8- (1-methylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-7- (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8- (1-methylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -8-ethoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -7- (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-bromo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -8-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -8-bromo-6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-trifluoromethoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -8-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -5,7-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -7,8-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -7-isopropyloxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -8-phenyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -7,8-dimethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6,8-bis (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -7-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -7- (1-methylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -7-phenyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-7-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -8-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-7-petyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6,7-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6,8-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6,8-dibromo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6,8-dimethoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-nitro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-amino-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -ethyl 6-amino-2-trifluoromethyl-2H-1-benzopyran-3-carboxylate; (S) -6-chloro-8-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -8-chloro-6-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -8-chloro-6-methoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6,8-difluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-bromo-8-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -8-bromo-6-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -8-bromo-6-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -8-bromo-5-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-bromo-8-methoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -7- (N, N-diethylamino) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-[[(phenylmethyl) amino] sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-[(dimethylamino) sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-aminosulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6- (methylamino) sulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-[(4-morpholino) sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-[(1,1-dimethylethyl) aminosulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-[(2-methylpropyl) aminosulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-methylsulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -8-chloro-6-[[(phenylmethyl) amino] sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-N, N-diethylaminosulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-phenylacetyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6- (2,2-dimethylpropylcarbonyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6,8-dichloro-7-methoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-2-trifluoromethyl-2H-1-benzothiopyran-3-carboxylic acid; (S) -6-[[(2-furanylmethyl) amino] sulfonyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-[(phenylmethyl) sulfonyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-[[(phenylethyl) amino] sulfonyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-iodo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -8-bromo-6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-formyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8-formyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-bromo-7- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -5,6-dichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-cyano-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-hydroxymethyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (difluoromethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -2,6-bis (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -5,6,7-trichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6,7,8-trichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (methylthio) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (methylsulfinyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -5,8-dichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (pentafluoroethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -2- (trifluoromethyl) -6-[(trifluoromethyl) thio] -2H-1-benzothiopyran-3-carboxylic acid; (S) -6,8-dichloro-7-methyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-2,7-bis (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -5-methoxy-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-benzoyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (4-chlorobenzoyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (4-hydroxybenzoyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-phenoxy-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -8-chloro-6- (4-chlorophenoxy) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -2- (trifluoromethyl) -6- [4- (trifluoromethyl) phenoxy) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (4-methoxyphenoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (3-chloro-4-methoxyphenoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (4-chlorophenoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -8-chloro-2- (trifluoromethyl) -6- [4- (trifluoromethyl) phenoxy] -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8-cyano-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8-[(hydroxyimino) methyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8- (hydroxymethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -8- (1H-benzimidazol-2-yl) -6-chloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -7- (1,1-dimethylethyl) -2- (pentafluoroethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8- (methoxymethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8- (benzyloxymethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8-ethenyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8-ethynyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8- (2-thienyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8- (2-furanyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8- (5-chloro-1-pentynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8- (1-pentynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8- (phenylethynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8- (3,3-dimethyl-1-butynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8-[(4-chlorophenyl) ethynyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8-[(4-methoxyphenyl) ethynyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (phenylethynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8- (4-chlorophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8- (3-methoxyphenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8-[(4-methylthio) phenyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8-[(4-methylsulfonyl) phenyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8-phenyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-bromo-8-fluoro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (4-fluorophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-phenyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -8-chloro-6-fluoro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6,8-diiodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (5-chloro-2-thienyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (2-thienyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (4-chlorophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (4-bromophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (ethynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-methyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8- (4-methoxyphenyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-2- (trifluoromethyl) -4-ethenyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-2- (trifluoromethyl) -4-phenyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-4- (2-thienyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6- (2,2,2-trifluoro-1-hydroxyethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; (S) -6,8-dimethyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; (S) -6- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; (S) -7-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; (S) -6,7-dimethyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; (S) -8-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; (S) -2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; (S) -6-chloro-7-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; (S) -7-chloro-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; (S) -6,7-dichloro-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; (S) -2- (trifluoromethyl) -6-[(trifluoromethyl) thio] -2H-1-benzothiopyran-3-carboxylic acid; (S) -6,8-dichloro-2-trifluoromethyl-2H-1-benzothiopyran-3-carboxylic acid; (S) -6-chloro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; (S) -6,8-dichloro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; (S) -6,7-difluoro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; (S) -6-iodo-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; (S) -6-bromo-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; (S) -1,2-dihydro-6- (trifluoromethoxy) -2- (trifluoromethyl) -3-quinolinecarboxylic acid; (S) -6- (trifluoromethyl) -1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; (S) -6-cyano-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; (S) -6-chloro-1,2-dihydro-1-methyl-2- (trifluoromethyl) -3-quinolinecarboxylic acid; (S) -6-chloro-1,2-dihydro-2- (trifluoromethyl) -1-[[4- (trifluoromethyl) phenyl] methyl] -3-quinolinecarboxylic acid; (S) -6-chloro-1-[(4-chlorophenyl) methyl] -1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; (S) -6-chloro-1,2-dihydro-2- (trifluoromethyl) -1-[[4- (methoxy) phenyl] methyl] -3-quinolinecarboxylic acid; (S) -6-chloro-1-[(4-cyanophenyl) methyl] -1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; (S) -6-chloro-1,2-dihydro-1-[(4-nitrophenyl) methyl] -2- (trifluoromethyl) -3-quinolinecarboxylic acid; (S) -6-chloro-1,2-dihydro-1-ethyl-2- (trifluoromethyl) -3-quinolinecarboxylic acid; (S) -6-chloro-2- (trifluoromethyl) -1,2-dihydro [1,8] naphthyridine-3-carboxylic acid; (S) -2-trifluoromethyl-2H-naphtho [1,2-b] pyran-3-carboxylic acid; (S) -2-trifluoromethyl-3H-naphtho [2,1-b] pyran-3-carboxylic acid; (S) -2-trifluoromethyl-2H-naphtho [2,3-b] pyran-3-carboxylic acid; (S) -5- (hydroxymethyl) -8-methyl-2- (trifluoromethyl) -2H-pyrano [2,3-c] pyridine-3-carboxylic acid; The term "hydrido" refers to only one hydrogen atom (H). This hydrido radical may, for example, be attached to an oxygen atom to form a hydroxyl radical, or two hydrido radicals may be attached to a carbon atom to form a methylene (—CH 2 —) radical. When the term "alkyl" is used alone or within other terms such as "haloalkyl" and "alkylsulfonyl", 1 to about 20 carbon atoms or preferably 1 to about 12 carbon atoms Having straight or branched chain radicals. More preferred alkyl radicals are "lower alkyl" radicals having 1 to 6 carbon atoms. Examples of such radicals include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, iso-amyl, hexyl and the like. Most preferred are lower alkyl radicals having 1 to 3 carbon atoms. The term "alkenyl" includes straight or branched chain radicals having 2 to about 20 carbon atoms or at least 2 to about 12 carbon atoms having at least one carbon-carbon double bond. More preferred alkenyl radicals are "lower alkenyl" radicals having 2 to about 6 carbon atoms. Examples of alkenyl radicals include ethyl, propenyl, allyl, butenyl and 4-methylbutenyl. The term "alkynyl" refers to a straight or branched chain radical having 2 to about 20 carbon atoms or preferably 2 to about 12 carbon atoms. More preferred alkynyl radicals are "lower alkynyl" radicals having 2 to about 10 carbon atoms. Most preferred are "lower alkynyl" radicals having 2 to about 6 carbon atoms. Examples of such radicals include propargyl, butynyl and the like. The terms "alkenyl" and "lower alkenyl" include radicals having "cis" and "trans" coordination, or optionally "E" and "Z" coordination. The term "halo" means a halogen such as fluorine, chlorine, bromine or iodine atoms. The term "haloalkyl" includes radicals in which any one or more alkyl carbon atoms are substituted with halo as defined above. Particularly included are monohaloalkyl, dihaloalkyl and polyhaloalkyl radicals. Monohaloalkyl radicals may have any of the iodo, bromo, chloro or fluorine atoms in the radical, for example. Dihalo and polyhaloalkyl radicals may be a combination of two or more identical halo atoms with the same or different halo radicals. "Lower haloalkyl" includes radicals having 1 to 6 carbon atoms. Examples of haloalkyl radicals include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoroethyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoro Propyl, dichloroethyl and dichloropropyl. "Perfluoroalkyl" means an alkyl radical in which all hydrogen atoms are replaced with fluorine atoms. Examples include trifluoromethyl and pentafluoroethyl. The term "hydroxyalkyl" includes straight or branched chain alkyl radicals having 1 to about 10 carbon atoms, any of which may be substituted with one or more hydroxyl radicals. More preferred hydroxyalkyl radicals are "lower hydroxyalkyl" radicals having 1 to 6 carbon atoms and having one or more hydroxyl radicals. Examples of such radicals include hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl and hydroxyhexyl. The term “cyanoalkyl” includes straight or branched chain alkyl radicals having 1 to about 10 carbon atoms, any of which may be substituted with one cyano radical. More preferred cyanoalkyl radicals are "lower cyanoalkyl" radicals having 1 to 6 carbon atoms and one cyano radical. Examples of such radicals include cyanomethyl. The term "alkoxy" includes straight or branched chain oxygen containing radicals each having an alkyl moiety of 1 to about 10 carbon atoms. More preferred alkoxy radicals are "lower alkoxy" radicals having 1 to 6 carbon atoms. Examples of such radicals include methoxy, ethoxy, propoxy, butoxy and tert-butoxy. “Alkoxy” radicals may be further substituted with one or more halo atoms such as fluorine, chloro or bromo to provide a “haloalkoxy” radical. Examples of such radicals include fluoromethoxy, chloromethoxy, trifluoromethoxy, trifluoroethoxy, fluoroethoxy and fluoropropoxy. The term "aryl" includes aromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl, indane and biphenyl. The above "aryl" group may have 1 to 3 substituents such as lower alkyl, hydroxy, halo, haloalkyl, nitro, cyano, alkoxy and lower alkylamino. The term "heterocycleyl" includes saturated, partially saturated and unsaturated heteroatom-containing cyclic radicals, wherein the heteroatom may be selected from nitrogen, sulfur and oxygen. Examples of saturated heterocyclic radicals include saturated 3-6 membered heteromonocycle groups containing 1-4 nitrogen atoms [e.g. pyrrolidinyl, imidazolidinyl, piperidino, pipera Genyl]; Saturated 3-6 membered heteromonocycle groups [eg, morpholinyl] containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms; And saturated 3-6 membered heteromonocycle groups (eg, thiazolidinyl) containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms. Examples of partially saturated heterocyclyl radicals include dihydrothiophene, dihydropyran, dihydrofuran and dihydrothiazole. Examples of unsaturated heterocyclyl radicals, alias “heteroaryl” radicals, include, for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidyl, 1-5, such as pyrazinyl, pyridazinyl, triazolyl [eg, 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl] Unsaturated 5-6 membered heterocyclyl group containing two nitrogen atoms; For example, indolyl, isoindolyl, indolinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl, tetrazolopyridazinyl [eg, tetrazolo [1,5-b] pyrida Unsaturated condensed heterocycle group containing 1 to 5 nitrogen atoms, such as genyl]; For example, unsaturated 3-6 membered heteromonocycle group containing oxygen atoms, such as pyranyl, 2-furanyl, 3-furanyl, etc .; For example, unsaturated 5-6 membered heteromonocyclic group containing a sulfur atom, such as 2-thienyl, 3-thienyl, etc .; 1-2, for example, oxazolyl, isooxazolyl, oxdiazolyl [eg, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl] Unsaturated 5-6 membered heteromonocycle group containing 3 oxygen atoms and 1 to 3 nitrogen atoms; Unsaturated condensed heteromonocycle groups containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [eg, benzoxazolyl, benzoxadiazolyl]; 1 to 2 sulfur atoms such as, for example, thiazolyl, thiadiazolyl [eg, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl] and Unsaturated 5-6 membered heteromonocycle groups containing 1 to 3 nitrogen atoms; And unsaturated condensed heterocycle groups containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms [eg, benzothiazolyl, benzothiadiazolyl]. The term also includes radicals when the heterocycle radical is fused with an aryl radical. Examples of such fused bicyclic radicals include benzofuran, benzothiophene and the like. The above "heterocycleyl" group may have 1 to 3 substituents, such as lower alkyl, hydroxy, oxo, amino and lower alkylamino. Examples of preferred heterocyclic radicals include 5-10 membered fused or unfused radicals. More preferred examples of heteroaryl radicals include benzofuryl, 2,3-dihydrobenzofuryl, benzothienyl, indolyl, dihydroindolyl, chromanyl, benzopyran, thiochromenyl, benzothiopyran, benzodioxolyl, benzo Dioxanyl, pyridyl, thienyl, thiazolyl, oxazolyl, furyl and pyrazinyl. The term "sulfonyl", either alone or in combination with other terms such as alkylsulfonyl, cools each divalent radical -SO 2- . "Alkylsulfonyl" is as defined above. The same alkyl radical includes those attached to sulfonyl radicals. More preferred alkylsulfonyl radicals are "lower alkylsulfonyl" radicals having 1 to 6 carbon atoms. Examples of such lower alkylsulfonyl radicals include methylsulfonyl, ethylsulfonyl and propylsulfonyl. "Haloalkylsulfonyl" includes those in which a haloalkyl radical as defined above is attached to a sulfonyl radical. More preferred haloalkylsulfonyl radicals are "lower haloalkylsulfonyl" radicals having 1 to 6 carbon atoms. Examples of such lower haloalkylsulfonyl radicals include trifluoromethylsulfonyl. The term "arylalkylsulfonyl" includes aryl radicals as defined above attached to an alkylsulfonyl radical. Examples of such radicals include benzylsulfonyl and phenylethylsulfonyl. The terms "sulfamyl", "aminosulfonyl" and "sulfonamidyl" are used alone or in "N-alkylaminosulfonyl", "N-arylaminosulfonyl", "N, N-dialkyl As used herein, such as in aminosulfonyl "and" N-alkyl-N-arylaminosulfonyl ", refers to the sulfonyl radical being substituted with an amine radical to form sulfonamide (-SO 2 NH 2 ). The term "alkylaminosulfonyl" includes "N-alkylaminosulfonyl" and "N, N-dialkylaminosulfonyl", wherein the sulfamoyl radicals each represent one alkyl radical, or two alkyl radicals. It is substituted. More preferred alkylaminosulfonyl radicals are "lower alkylaminosulfonyl" radicals having 1 to 6 carbon atoms. Examples of such lower alkylsulfonyl radicals include N-methylaminosulfonyl, N-ethylaminosulfonyl and N-methyl-N-ethylaminosulfonyl. The terms " N-arylaminosulfonyl " and " N-alkyl-N-arylaminosulfonyl " respectively cool the sulfamyl radicals substituted with one aryl radical or one alkyl and one aryl radical. More preferred N-alkyl-N-arylaminosulfonyl radicals are "lower N-alkyl-N-arylaminosulfonyl" radicals having alkyl radicals of 1 to 6 carbon atoms. Examples of such lower N-alkyl-N-arylaminosulfonyl radicals include N-methyl-N-phenylaminosulfonyl and N-ethyl-N-phenylaminosulfonyl. Examples of such N-aryl-aminosulfonyl radicals include N-phenylaminosulfonyl. The term "arylalkylaminosulfonyl" includes aralkyl radicals as defined above attached to aminosulfonyl radicals. The term "heterocyclylaminosulfonyl" includes heterocyclyl radicals as defined above attached to aminosulfonyl radicals. The term "carboxy" or "carboxyl", when used alone or in combination with other terms such as "carboxyalkyl", refers to -CO 2 H. The term "carboxyalkyl" includes radicals having a carboxy radical as defined above attached to an alkyl radical. The term "carbonyl", used alone or in combination with other terms such as "alkylcarbonyl", cools-(C = O)-. The term "acyl" optionally cools the radicals provided by the residues after removal of the hydroxyl from the organic acid. Examples of such acyl radicals include alkanoyl and aroyl radicals. Formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, trifluoroacetyl of such lower alkanoyl radicals. The term "aroyl" includes aryl radicals having carbonyl radicals as defined above. Examples of the aroyl include benzoyl, naphthoyl, and the like, and the aryl in the aroyl may be further substituted. The term "alkylcarbonyl" includes radicals having carbonyl radicals substituted with alkyl radicals. More preferred alkylcarbonyl radicals are "lower alkylcarbonyl" radicals having 1 to 6 carbon atoms. Examples of such radicals include methylcarbonyl and ethylcarbonyl. More preferred haloalkylcarbonyl radicals are "lower haloalkylcarbonyl" radicals having 1 to 6 carbon atoms. Examples of such radicals include trifluoromethylcarbonyl. The term "arylcarbonyl" includes radicals having carbonyl radicals substituted with aryl radicals. Further preferred arylcarbonyl radicals include phenylcarbonyl. The term "heteroarylcarbonyl" includes radicals having a carbonyl radical substituted with a heteroaryl radical. The term "arylalkylcarbonyl" includes radicals having carbonyl radicals substituted with arylalkyl radicals. Further preferred arylcarbonyl radicals include benzylcarbonyl. The term "heteroarylalkylcarbonyl" includes radicals having carbonyl radicals substituted with heteroarylalkyl radicals. The term "alkoxycarbonyl" means a radical comprising an alkoxy radical attached to a carbonyl radical as defined above via an oxygen atom. Preferably, "lower alkoxycarbonyl" includes alkoxy radicals having 1 to 6 carbon atoms. Examples of such "lower alkoxycarbonyl" ester radicals include substituted or unsubstituted methoxy carbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl and hexyloxycarbonyl. The term "aminocarbonyl" is used alone or in "aminocarbonylalkyl", "N-alkylaminocarbonyl", "N-arylaminocarbonyl", "N, N-dialkylaminocarbonyl" Used with other terms such as "N-alkyl-N-arylaminocarbonyl", "N-alkyl-N-hydroxyaminocarbonylalkyl" and "N-alkyl-N-hydroxyaminocarbonyl" In the case, it refers to the group -C (= 0) NH 2 . The terms "N-alkylaminocarbonyl" and "N, N-dialkylaminocarbonyl" carry coolly the aminocarbonyl radicals substituted with one alkyl radical and two alkyl radicals, respectively. More preferred are "lower alkylaminocarbonyls" having lower alkyl radicals as defined above attached to aminocarbonyl radicals. The terms "N-arylaminocarbonyl" and "N-alkyl-N-arylaminocarbonyl" refer to aminocarbonyl radicals each substituted with one aryl radical or one alkyl and one aryl radical. The term “N-cycloalkylaminocarbonyl” optionally cools an aminocarbonyl radical substituted with at least one cycloalkyl radical. More preferred are "lower cycloalkylaminocarbonyls" having lower cycloalkyl radicals of 3 to 7 carbon atoms attached to the aminocarbonyl radicals. The term "aminoalkyl" includes alkyl radicals substituted with amino radicals. The term "alkylaminoalkyl" includes aminoalkyl radicals having nitrogen atoms substituted with alkyl radicals. The term "heterocycleylalkyl" includes heterocycles substituted with alkyl radicals. More preferred heterocyclylalkyl radicals are "5- or 6-membered heteroarylalkyl" radicals having an alkyl moiety of 1 to 6 carbon atoms and a 5- or 6-membered heteroaryl radical. Examples include radicals such as pyridylmethyl and thienylmethyl. The term "aralkyl" includes aryl substituted alkyl radicals. Preferred aralkyl radicals are "lower aralkyl" radicals having aryl radicals attached to alkyl radicals having 1 to 6 carbon atoms. Examples of such examples include benzyl, diphenylmethyl and phenylethyl. Aryl in the aralkyl described above may be additionally substituted with halo, alkyl, alkoxy, haloalkyl and haloalkoxy. The term "arylalkenyl" includes aryl substituted alkenyl radicals. Preferred arylalkenyl radicals are "lower arylalkenyl" radicals having aryl radicals attached to alkenyl radicals having 2 to 6 carbon atoms. Examples of such radicals include phenylethenyl. Aryl in the arylalkenyl described above may be additionally substituted with halo, alkyl, alkoxy, haloalkyl and haloalkoxy. The term "arylalkynyl" includes aryl-substituted alkynyl radicals. Preferred arylalkynyl radicals are "lower arylalkynyl" radicals having aryl radicals attached to alkynyl radicals having 1 to 6 carbon atoms. Examples of such radicals include phenylethynyl. Aryl in the aralkyl described above may be additionally substituted with halo, alkyl, alkoxy, haloalkyl and haloalkoxy. The terms benzyl and phenylmethyl may be used interchangeably. The term "alkylthio" includes radicals comprising straight or branched chain alkyl radicals of 1 to 10 carbon atoms attached to a divalent sulfur atom. Examples of "alkylthio" are methylthio, (CH 3 -S-). The term "haloalkylthio" includes radicals comprising haloalkyl radicals of 1 to 10 carbon atoms attached to a divalent sulfur atom. An example of "haloalkylthio" is trifluoromethylthio. The term "alkylsulfinyl" includes radicals comprising straight or branched chain alkyl radicals of 1 to 10 carbon atoms attached to a divalent -S (= 0)-atom. The term "arylsulfinyl" includes radicals that include an aryl radical attached to a divalent -S (= 0)-atom. The term "haloalkylsulfinyl" includes radicals comprising haloalkyl radicals of 1 to 10 carbon atoms attached to a divalent -S (= 0)-atom. The terms "N-alkylamino" and "N, N-dialkylamino" refer to amino groups each substituted with one alkyl radical and two alkyl radicals. More preferred alkylamino radicals refer to "lower alkylamino" radicals having one or two alkyl radicals of 1 to 6 carbon atoms attached to a nitrogen atom. Suitable "alkylamino" may be mono or dialkylamino such as N-methylamino, N-ethylamino, N, N-dimethylamino, N, N-diethylamino and the like. The term "arylamino" optionally cools an amino group substituted with one or two aryl radicals, such as N-phenylamino. An "arylamino" radical may be further substituted by the aryl ring portion of this radical. The term "heteroarylamino" refers to an amino group substituted with one or two heteroaryl radicals, such as N-thienylamino. The "heteroarylamino" radical may be further substituted by the aryl ring portion of this radical. The term "aralkylamino" refers to an amino group substituted with one or two aralkyl radicals, such as N-benzylamino. An "aralkylamino" radical may be further substituted by the aryl ring portion of this radical. The terms "N-alkyl-N-arylamino" and "N-aralkyl-N-alkylamino" are each substituted with one aralkyl and one alkyl radical, or one aryl and one alkyl radical, in an amino group. Refer to amino group. The term "arylthio" includes aryl radicals of 6 to 10 carbon atoms attached to divalent sulfur atoms. Examples of "arylthio" include phenylthio. The term "aralkylthio" includes aralkyl radicals as defined above attached to divalent sulfur atoms. Examples of "aralkylthio" include benzylthio. The term "aralkylsulfonyl" includes aralkyl radicals as defined above attached to bivalent sulfonyl radicals. The term “heterocyclylsulfonyl” includes heterocyclyl radicals as defined above attached to a divalent sulfonyl radical. The term "aryloxy" includes aryl radicals as defined above attached to an oxygen atom. Examples of such radicals include phenoxy. The term "aralkoxy" includes oxygen containing aralkyl radicals that are attached to another radical via an oxygen atom. More preferred aralkoxy radicals are "lower alkoxy" radicals with phenyl radicals attached to lower alkoxy radicals as defined above. The present invention includes a pharmaceutical composition consisting of a therapeutically effective amount of a compound of formula I and at least one pharmaceutically acceptable carrier, adjuvant or diluent associated therewith. The invention also includes a method of treating a patient with a cyclooxygenase-2 mediated disease, such as inflammation, which method provides a pharmacologically acceptable amount of Formula I to a patient who has or is susceptible to such a disease. Consists of treating with a compound. In addition, the stereoisomers are included in the compound family of the formula (I). The compounds of the present invention may have one or more asymmetric carbons and therefore may exist in the form of racemic or non-racemic mixtures as well as in optical isomers. Thus, some compounds of the present invention may exist as racemic mixtures, which are also included in the present invention. Optical isomers are conventional, for example, by treatment with optically active bases to form diastereoisomeric salts, which are then crystallized to separate mixtures of enantiomers, and then free optically active bases from these salts. By dividing the racemic mixture according to the phosphorus process. Examples of suitable bases are brucin, strynnin, dihydroabiethylamine, quinine, ccinronidine, ephedrine, α-methylbenzylamine, amphetamine, deoxyphedrine, chloramphenicol intermediate, 2-amino-1-butanol and 1- ( 1-naphthyl) ethylamine. Another method for the separation of optical isomers is carried out using a chiral chromatographic column that is optimally selected to maximize the separation of enantiomers. Another useful method involves the synthesis of divalent enantiomers. Synthesized enantiomers can be separated by conventional methods such as chromatography, distillation, crystallization or sublimation and then hydrolyzed enantiomerically to liberate compounds of purity. Optically active compounds of formula I may be readily obtained by using optically active starting materials. These isomers can be free acids, free bases, esters or salts. Additional methods of resolving optical isomers, known to those skilled in the art, can be used, for example, as discussed by J. Jaques et al. In Enantiomers, Racemates, and Resolutions (John Wiley and Sons, New York (1981)). This can be used. Also included in the class of compounds of Formulas I and I 'are the amide protecting acids. Thus, primary and secondary amines can react with the chromene-3-carboxylic acids of formulas I and I 'to form amides that can be useful as prodrugs. Preferred amines include heterocyclic amines including optionally substituted aminothiazole, optionally substituted amino-isoxazole, and optionally substituted aminopyridine; Aniline derivatives; Sulfonamides; and the like. In addition, 1-acyldihydroquinolines can function as prodrugs for 1H-dihydroquinolines. In addition, the family of compounds of Formulas I and I 'include pharmacologically acceptable salts. The term "pharmacologically acceptable salt" includes salts commonly used for forming free salts or addition salts of free acids or free salts or for forming alkali metal salts. The nature of the salt is not limited as long as it is pharmacologically acceptable. Suitable pharmacologically acceptable acid addition salts of compounds of formula I can be prepared from inorganic acids or from organic acids. Examples of such inorganic acids include hydrochloric acid, bromic acid, iodic acid, nitric acid, carbonic acid, sulfuric acid and phosphoric acid. Suitable organic acids may be selected from aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxyl and sulfonic families of organic acids, examples of which are formic acid, acetic acid, propionic acid, succinic acid, glycolic acid, gluconic acid, lactic acid. , Malic acid, tartaric acid, citric acid, ascorbic acid, glucuronic acid, maleic acid, fumaric acid, pyruvic acid, asphalt acid, glutamic acid, benzoic acid, geranillic acid, mesyline acid, salicylic acid, 4-hydroxy Benzoic acid, phenylacetic acid, mandeline acid, embonine (famoin) acid, methanesulfonic acid, ethanesulfonic acid, benbensulfonic acid, pantotheic acid, 2-hydroxyethanesulfonic acid, toluenesulfonic acid, sulfanilinic acid, cyclohexylaminosulfonic acid And stearic acid, alzenic acid, β-hydroxybutyric acid, salicylic acid, galactinic acid and galacturonic acid. Suitable pharmacologically acceptable base addition salts of the compounds of formulas I and I 'include metal salts such as salts made from aluminum, calcium, lithium, magnesium, potassium, sodium and zinc, or caffeine, arginine, diethylamine Substituted amines including cyclic amines such as N-ethyl piperidine, histidine, glucamine, isopropylamine, lysine, morpholine, N-ethyl morpholine, piperazine, piperidine, triethylamine and trimethylamine And salts made from organic bases including primary, secondary and tertiary amines. All these salts can be prepared by conventional means from the compounds corresponding to the invention, for example by reacting the compound of formula I or I 'with the appropriate acid or base. Whole compounding process Compounds of the present invention can be synthesized according to the schemes of Schemes 1-16 below, wherein the R 1 -R 6 substituents are as defined in Formulas I-II above, unless otherwise noted. Scheme 1 illustrates a general method for the preparation of a wide variety of substituted 2H-1-benzopyran derivatives (3,4). In step 1, the illustrated ortho-hydroxybenzaldehyde (salicyaldehyde) derivative 1 is acrylate in the presence of a base such as potassium carbonate in a solvent such as dimethylformamide to provide the necessary 2H-1-benzopyran ester 3 Condensed with derivative 2. Other base-solvent bonds for this condensation include solvents such as dimethyl sulfoxide and organic salts such as triethylamine. In step 2, the ester is acidified and then treated with the corresponding acid as treated with an aqueous base (sodium hydroxide) in a suitable solvent such as ethanol to give substituted 2H-1-benzopyran-3-carboxylic acid 4. Hydrolysis. Synthetic Scheme 2 shows a general method for functionalizing selected 2H-1-benzopyrans. Treatment of 2H-1-benzopyran carboxylic acid 4 or ester 3 with an electrophilic agent produces 6-substituted 2H-1-benzopyran 5. A wide variety of electrophiles react selectively with 2H-1-benzopyran 4 at the 6-position to provide analogs in high yield. Electrophiles such as halogens (chlorine or bromine) provide 6-halo derivatives. Chlorosulfonic acid reacts to provide 6-position sulfonyl chloride which can be further converted to sulfonamide or sulfone. Friedel-Craft acylation of 4 gives 6-acylated 2H-1-benzopyran in very good yield. Many other electrophiles can be used to selectively react with these 2H-1-benzopyrans in a similar manner. The 6-position substituted 2H-1-benzopyran can be reacted with the electrophilic reactant at the 8-position using a chemical reaction similar to that described above for the 6-position of the valence substitution. This yields substituted 2H-1-benzopyrans at both 6 and 8 positions. Synthesis Scheme 3 illustrates a second general synthesis of substituted 2H-1-benzopyran-3-carboxylic acids allowing substitution at position 4 of 2H-1-benzopyran. In this case, commercially or synthetically available substituted ortho-hydroxy acetophenone 6 is treated with two or more equivalents of strong bases such as lithium bis (trimethylsilyl) amide in a solvent such as tetrahydrofuran (THF). Then react with diethylcarbonate to give beta-keto ester 7. Ester 7 is condensed with an acid chloride or anhydride by heating in a solvent such as toluene in the presence of a base such as potassium carbonate to give 4-oxo-4H-1-benzopyran 8. By catalytic reduction with palladium on charcoal and hydrogen gas in a solvent such as ethanol to produce a new beta-keto ester 9 (of the dual structure shown) or by the use of triethylsilane in a solvent such as trifluoroacetic acid. Alternatively, the olefins can be reduced by various formulations comprising sodium borohydride (NaBH 4 ) in a solvent mixture such as ethanol and THF. Oxylation of oxygen of ketone enolation in the presence of a base such as 2,6-di-tert-butyl-4-methylpyridine and the use of an acylating agent such as trichloromethanesulfon anhydride and a solvent such as methylene chloride Create treeplate 10 The triflate 10 is reduced to a reactant such as a palladium (0) catalyst such as tetrakis (triphenylphosphine) palladium (0), tri-n-butyltin hydride, lithium chloride in a solvent such as tetrahydrofuran and R 2H-1-benzopyran ester 11, which is “Hydrogen, can be produced. Said ester 11 is saponified with a base such as 2.5 N sodium hydroxide in a mixed solvent such as tetrahydrofuran-ethanol-water (7: 2: 1). To produce the required substituted 2H-1-benzopyran-3-carboxylic acid. Carbon Fragment R3To In order to coalesce, known reactants for "cross-coupling" such as lithium chloride and tributylethylenyltin with a palladium (0) catalyst such as tetrakis (triphenylphosphine) palladium in a solvent such as tetrahydrofuran Treated with trilate 10 with 2H-1-benzopyran ester 11 (where R3Is the vinyl share). Ester 6 is required to be saponified with a base such as 2.5 N sodium hydroxide in a mixed solvent such as tetrahydrofuran-ethanol-water (7: 2: 1) to give 4-vinyl-2H-1-benzopyran-3-carbosyl. Acid (12, R "= CH3CH-) can be generated. Similarly, triflate 10 is prepared using tri-n-butylphenyltin under similar conditions.3Can be converted to 2H-1-benzopyran, which is phenyl, and by hydrolysis of the ester R3= Phenyl which can be converted to carboxylic acid 12. Using a similar method, substituent R3May be substituted with an olefin, an aromatic compound, a heteroaryl, an acetylene and an acetylene, so that the substituents may be coalesced. Synthetic Scheme 4 shows another general procedure for preparing 4-oxo-4H-1-benzopyran 8. ortho-fluorobenzoyl chloride is treated with beta-keto ester 14 which is suitably substituted with a base such as potassium carbonate in a solvent such as toluene to give 4-oxo- suitably 4H-1-benzopyran 8. 4-oxo-4H-1-benzopyran 8 may be converted to 2H-1-benzopyran 12 as described in Scheme 3. Synthesis Scheme 5 shows a general method for the substitution of an aromatic ring of 2H-1-benzopyran. This is an organo-palladium mediated "cross-coupling" using a palladium (0) catalyst to link benzopyran 15 to acetylene, olefin, nitrile or aryl coupling agents at position Y where Y is iodide, bromide or triflate "Through the compound. Substituted acetylenes as coupling agents will provide the corresponding substituted acetylenes. Substituted aryl shares can be incorporated using arylboronic acid or esters, and nitriles can be incorporated using zinc (II) cyanide. The resulting ester 16 can be converted to carboxylic acid 17 as described in Scheme 1. Another approach to substitution of the aryl quotient of benzopyran 15 is to convert Y, either iodide or bromide, to perfluoroalkyl quotient. An example of this conversion is the conversion of 15 (Y = iodide) to 16 (R 3 = pentafluoroethyl) in hexamethylphosphoamide (HMPA) using copper (I) iodide and tentafluoropropionate. to be. The resulting ester 16 can be converted to carboxylic acid 15 as described in Scheme 1. In a similar manner, the aromatic ring adds substitution of dihydroquinolane-3-carboxylates. This can be achieved through organopalladium linkages of various coupling agents with triflate or aryliodide and bromide (P. Heck's, organic synthetic palladium reactant, Academic Press 1985). When using a suitable palladium catalyst such as tetrakis (triphenyl-phosphine) palladium (0) in this reaction, coupling agents such as alkynes provide dispersed alkynes, phenylboronic acid confer biphenyl compounds and cyanide Produces an arylcyano compound. In a similar manner a number of other palladium catalysts and coupling agents can be used to selectively react with suitably substituted dihydroquinoline-3-carboxylates. Synthesis Scheme 6 shows a general method for synthesizing the substituted salicylates with suitable substituted phenols commercially or synthetically available. Several other methods using formaldehyde or chemically equivalent reactants are described in detail below. Corresponding salicyaldehyde 1 is produced by reacting appropriately substituted phenol 18 with formaldehyde (or chemical equivalent) in a basic medium. The intermediate ortho-hydroxymethylphenol 19 will be inherently oxidized to salicyaldehyde 1 under appropriate reaction conditions. The reaction is commonly used as a source of formaldehyde, toluene as a solvent (2 or more equivalents), toluene as a solvent, ethyl magnesium bromide as a base or magnesium methoxide (one equivalent), and hexamethylformamide (HMPA). ) Or N, N, N ', N'-tetramethylethylenediamine (TMEDA). (See Casiraghi, G. et al. J. C. S Perkin I, 1978, 318-321.) Alternatively, suitably substituted phenol 18 is reacted with formaldehyde under aqueous base conditions to form substituted ortho-hydroxybenzyl alcohol 19 (a) J. Leroy and C. Wakselman, J. Fluorine Chem. , 40. 23-32, 1998, b) AA Moshfegh et al., Helv. Chim. Acta., 65, 1229-1232, 1982). Commonly used bases include aqueous potassium carbonate or sodium carbonate. Formalin (38% aqueous formaldehyde solution) is commonly used as a source of formaldehyde. The resulting ortho-hydroxybenzyl alcohol 19 can be converted to salicylicaldehyde 1 by an oxidizing agent such as manganese (IV) dioxide in a solvent such as methylene chloride or chloroform (see Synthetic Commun. 24, et al., RG. 53-58, 1994). Suitably substituted phenol 18 can be treated with hexamethylenetetramine (HMTA) under acidic conditions to prepare salicylicaldehyde 1 (duff reaction; see Y. Suzuki and H. Takahashi, Chem. Pharm. Bull., 31, 1751-1753, 1983). This reaction often uses acids such as acetic acid, boric acid, methanesulfuric acid or trichloromethanesulfuric acid. A commonly used source of formaldehyde is hexamethylenetetramine. Synthesis Scheme 7 shows the Reimer-Tiemann reaction, where suitable substituted phenol 18, commercially or synthetically available, is reacted with chloroform under acidic conditions to produce substituted salicylicaldehyde 1. See Cragoe, EJ; Schultz, EM, US Patent 3 794 734, 1974. Synthesis Scheme 8 shows that suitably substituted salicylic acid 21, commercially or synthetically available, converts to salicylicaldehyde 1 via 2-hydroxybenzyl alcohol 19 as intermediate. Reduction of salicylic acid 21 may be accomplished with a hydrate reducing agent such as borane in a solvent such as tetrahydrofuran. Salicyaldehyde 1 is provided by treating the intermediate 2-hydroxybenzyl alcohol 19 with an oxidant such as manganese (IV) oxide in a solvent such as fluoroform or methylene chloride. Synthesis Scheme 9 illustrates a general synthetic process for preparing a wide variety of substituted 2- (trifluoromethyl) -2H-1-benzodiopyran-3-carboxylic acids (25). In step 1, substituted thiophenol 22, which is suitably commercially or synthetically available, uses ortho- as a base such as n-butyllithium using TMEDA (N, N, N ', N'-tetramethylethylenediamine). Metallated and then treated with dimethylformamide to give 2-mercaptobenzaldehyde 23. Condensation of acrylate 2 and 2-mercaptobenzaldehyde 23 in the presence of a base can be saponified in the presence of an aqueous salt to provide substituted 2H-1-benzodiopyran-3-carboxylic acid 25. Synthesis Scheme 10 shows a process for preparing substituted 2-mercaptobenzaldehyde from substituted salicylicaldehydes that are commercially or synthetically available. In step 1, the phenolic hydroxyl of salicylaldehyde 1 is suitably substituted thiocarbamoyl chloride such as N, N-dimethylthiocarbamoyl chloride in a solvent such as dimethylformamide using a salt such as triethylamine. Is converted to the corresponding 0-aryl thiocarbamate 26 by acylation. In step 2, 0-aryl thiocarbamate 26 is rearranged to S-arylthiocarbamate 27 when heated to 200 ° C. with or without a solvent such as N, N-dimethylaniline. See A. Levai, P. Sebok, Synth.Commun., 22 1735-1750, 1992). Hydrolysis of S-arylthiocarbamate 27 with a salt such as 2.5 sodium hydroxide in a solvent mixture such as ethanol and tetrahydrofuran yields 2-mercaptobenzaldehyde 23, which is substituted as described in Scheme 9. 2h-1-benzodiopyran-3-carboxylic acid 25. Synthesis Scheme 11 describes a general method for the preparation of a wide variety of dihydroquinoline-3-carboxylic acid derivatives 30. R 2 represents aromatic substitution of 2-aminobenzaldehyde 28 which is commercially and synthetically available. Said 2-amino-benzaldehyde derivative 28, wherein R 2 represents various substitutions, such as potassium carbonate, triethylamine, or diazbicyclo [2.2.2] undec-7-ene in a solvent such as dimethylformamide Condensation with acrylate derivative 2 in the presence of a salt to give dihydroquinoline-3-carboxylate ester 29. The ester 29 is saponified to the corresponding acid, such as by treatment with an aqueous inorganic salt, such as 2.5% sodium hydroxide, in a suitable solvent such as ethanol to give the required dihydroquinoline-3-carboxylic acid 30 after acidification. . Synthesis Scheme 12 shows the preparation of dihydroquinoline-3-carboxylic acid 30 from 2-aminobenzoic acid 31. R 2 represents aromatic substitution of 2-aminobenzoic acid 31 which is commercially available and synthetically available. The reduction to the required 2-aminobenzyl alcohol 32 from representative 2-aminobenzoic acid 31 is accomplished with a hydrate reducing agent such as borane in a solvent such as tetrahydrofuran. Treatment of 2-aminobenzyl alcohol 32, which is required with an oxidant such as manganese oxide in a solvent such as methylene chloride, provides a representative 2-aminobenzaldehyde 28 (CT Alabaster et al., J. Med. Chem. 31, 2048-2056, 1986). . 2-aminobenzaldehyde is converted to the required dihydroquinoline-3-carboxylic acid 30 as described in Scheme 11. Synthesis Scheme 13 describes a general method for the preparation of a wide variety of dihydroquinoline-3-carboxylic acid derivatives 30 from isatin 33. R 2 represents an aromatic substituent of Satin 33 which is commercially and synthetically available. The illustrated satin 33 is treated with a salt such as sodium hydroxide and a basic peroxide generated from a hydrogen peroxide to provide the necessary 2-aminobenzoic acid 31 as shown (MS Newman and MW Lougue, J. Org. Chem., 36, 1398-1401, 1971). 2-Aminobenzoic acid 31 is subsequently converted to the required dihydroquinoline-3-carboxylic acid derivative 30 as described in Synthesis Scheme 12. Synthesis Scheme 14 is another general method for the preparation of dihydroquinoline-3-carboxylic acid derivative 30. In step 1, substituted commercial aniline 34, which is available commercially or synthetically, can be treated with an acrylicated reagent such as pivaloyl chloride to produce amide 35. The ortho-dianions of amide 35 are prepared by treating amide 35 at low temperature with organo-lithium bases such as tert-butyllithium or n-butyllithium of tetrahydrofuran. The dianion is cooled by dimethylformamide to give acrylated-2-aminobenzaldehyde 36. (J. Turner, J. Org. Chem., 48, 3401-3408, 1983) Reaction of these aldehydes with acrylic salts in the presence of salts such as lithium hydrates, followed by subsequent reaction with aqueous inorganic salts, ethanol By hydrolysis, such as by treatment with an aqueous base (sodium hydroxide) in a suitable solvent, such as acidification, dihydroquinoline-3-carboxylic acid 30 is provided. Synthesis Scheme 15 shows a general method for alkylation of dihydroquinoline-3-carboxylate ester derivative 29. Dihydroquinoline-3-carboxylate esters with alkyl halides such as iodine in the presence of a base such as caustic (50% aqueous sodium hydroxide) and a phase transfer catalyst such as tetrabutylammonium iodide in a solvent such as dichloromethane Treatment of derivative 29 is included in the synthesis step. These conditions provide N-alkylated dihydroquinoline-3-carboxylate ester 37. Saponification of 37 with an aqueous salt affords N-alkylated-dihydroquinoline-3-carboxylic acid derivative 38. The following examples include detailed description of the preparation of the compound of formula I-II. These descriptions fall within the scope of the present invention and are intended to illustrate the general synthetic process described above which forms part of the present invention. These details are described for illustrative purposes only and are not intended to limit the scope of the invention. All parts are given in weight and temperatures are in degrees Celsius unless otherwise noted. All compounds represented by NMR spectrum match the designated structure. The following abbreviations are used. HCL-hydrochloric acid MgSO 4 -Magnesium Sulfate Na 2 SO 4 -Sodium Sulfate DMF-Dimethylformamide THF-Tetrahydrofuran NaOH-Sodium Hydroxide EtOH-Ethanol K 2 CO 3 -Potassium Carbonate CDCl 3 -Deuterated Chloroform CD 3 OD-Deuterated Methanol Et 2 O-diethyl ether EtOAc-ethyl acetate NaHCO 3 -Sodium Bicarbonate KHSO 4 -Potassium Sulfate NaBH 4 -Sodium borohydride TMEDA-Tetramethylethylenediamine HMTA-Hexamethylethylenediamine DMSO-Dimethyl Sulfoxide HMPA-Hexamethyl Phosphoric Triamide Example 1 6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl 6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid A mixture of 5-chlorosalicylaldehyde (20.02 g, 0.128 mole) and ethyl 4,4,4-trifluorocrotonate (23.68 g, 0.14 mole) was dissolved in anhydrous DMF, warmed to 60 ° C., and anhydrous K Treated with 2 C0 3 (17.75 g, 1.128 mole). This solution was kept at 60 ° C. for 20 hours, cooled to room temperature and diluted with water. This solution was extracted with ethyl acetate. The combined extracts were washed with brine, dried over anhydrous MgSO 4 , filtered and concentrated in vacuo to yield 54.32 g of oil. This oil was dissolved in 250 ml of methanol and 100 ml of water, then the white solid formed was separated by filtration, washed with water and dried in vacuo to yield an ester as a yellow solid (24.31 g, 62%): mp 62- 64 ℃. 1 H NMR (CDCl 3 / 90MHz ) 7.64 (s, 1H), 7.30-7.21 (m, 2H), 6.96 (d, 1H, J = Hz), 5.70 (q, 1H, J = Hz), 4.30 (q , 2H, J = 7.2 Hz), 1.35 (t, 3H, J = 7.2 Hz). Step 2. Preparation of 6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid The ester solution from step 1 (13.02 g, 42 mmol) was dissolved in 200 ml of methanol and 20 ml of water, treated with lithium hydroxide (5.36 g, 0.128 mole) and stirred at room temperature for 16 hours. The reaction mixture was acidified with 1.2N HCl, and then the solid formed was separated by filtration. The solid was washed with 200 ml of water and 200 ml of hexane and dried in vacuo to yield the title compound as a yellow solid (10.00 g, 85%): mp 181-184 ° C. Example 2 6- (methylthio) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of 5- (methylthio) salicylaldehyde Ethyl magnesium bromide (38 ml of a 3.0 mole solution in diethyl ether, 113.8 mmol) was cooled with an ice water electrolyzer. To this cooled solution was added a solution of 4- (methylthio) phenol (15.95 g, 113.8 mmol) in diethyl ether (30 ml) over 0.15 hours and the gas was allowed to release during the addition. The reaction was maintained at 0 ° C. for 0.5 hours and at room temperature for 0.5 hours and the addition funnel was replaced with a distillation head. Toluene (250 ml) and diethyl ether were removed by distillation from the reactor. The reaction was cooled and toluene (250 ml) and hexamethylphosphoramide (HMPA) (19.8 ml, 20.4 g, 113.8 mmol) were added and the resulting mixture stirred for 0.25 h. The distillation head was replaced with a condenser and paraformaldehyde (8.5 g, 284.4 mmol) was added. The reaction was heated to 90 ° C. for 3 hours. The reaction mixture was cooled to room temperature and acidified with 1N HCl to phase separate. The organic phase was washed with water, then brine, dried over MgSO 4 , filtered and concentrated in vacuo to give a yellow solid. This solid was purified by silica chromatography (hexane-ethyl acetate, 5: 1) to give salicyaldehyde as a yellow crystalline solid (6.01 g) with a purity suitable for use in the next reaction without further purification. Step 2. Preparation of ethyl 6- (methylthio) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate 5-Methylthiosalicylaldehyde (Step 1) (2.516 g, 14,96 mmol) was converted to dimethylformamide (3.5 ml), potassium carbonate salt (2.27 g, 16.45 mmol) and ethyl 4,4,4-trifluorocroto Add to Nate (3.3 ml, 3.8 g, 22.4 mmol). This mixture was heated to 65 ° C. for 3 hours. The reaction was cooled to room temperature, poured into H 2 O (50 ml) and extracted with diethyl ether (2 × 75 ml). The combined ether containing phases are washed with aqueous NaHCO 3 solution (3 × 50 ml), aqueous 2N HCl solution (3 × 50 ml), and brine (3 × 50 ml) respectively, dried over MgSO 4 , filtered and isooctane Diluted with and partially concentrated in vacuo to precipitate ethyl ester (2.863 g, 60%) as a yellow powder: mp 87.8-89.6 ° C. This ester was of a purity suitable for use without further purification. Step 3. Preparation of 6- (Methylthio) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid This ester (step 2) was hydrolyzed to form carboxylic acids by a similar method as described in step 2 of example 1: mp 166.3-167.9 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.87 (s , 1H), 7.43 (d, 1H, J = 2.2Hz), 7.33 (dd, 1H, J = 8.5, 2.4Hz), 6.98 (d, 1H, J = 8.5 Hz), 5.79 (q, 1H, J = 7.0 Hz), 2.48 (s, 3H). FABLRMS m / z 291 (M + H). ESHRMS m / z 289.0152 (M−H, calculated 289.0146). Analytical Calcd for C 12 H 9 F 3 O 3 S 1 : C, 49,66; H, 3.13; S, 11.05. Found: C, 49.57; H, 3.02; S, 11.37. Example 3 7-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 3-Methylphenol was converted to the title compound by a method similar to that described in Example 2: mp 202.1-203.1 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.84 (s, 1H), 7.12 (d, 1H, J = 8.3Hz), 6.82 (m, 2H), 5.65 (q, 1H, J = 6.8Hz), 2.35 (s , 3H). FABLRMS m / z 259 (M + H). FABHRMS m / z 259.0576 (M + H, calculated 259.0582). Analytical Calcd for C 12 H 9 F 3 O 3 : C, 55.82; H, 3.51. Found: C, 55.93; H, 3.59. Example 4 2,7-bis (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 3- (trifluoromethyl) phenol was converted to the title compound by a method similar to that described in Example 2: mp 190.3-193.5 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.98 (s , 1H), 7.73 (d, 1H, J = 7.9Hz), 7.46 (d, 1H, J = 7.9Hz), 7.36 (s, 1H), 5.93 (q, 1H, J = 7.1 Hz). FABLRMS m / z 313 (M + H). FABHRMS m / z 313.0267 (M + H, calculated 313.0299). Analytical Calcd for C 12 H 6 F 6 O 3 : C, 46.17; H, 1.94. Found: C, 46.25; H, 2.00. Example 5 7-Bromo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 3-Bromophenol was converted to the title compound by a method similar to that described in Example 2: mp 198.4-199.5 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.89 (s , 1H), 7.43 (d, 1H, J = 8.1Hz), 7.31 (s, 1H), 7.30 (d, 1H, J = 8.1Hz), 5.84 (q, 1H, J = 7.1 Hz). FABLRMS m / z 323 (M + H). Analytical Calcd for C 11 H 6 BrF 3 O 3 : C, 40.90; H, 1.87. Found: C, 41.00; H, 1.85. Example 6 6-chloro-7-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 4-chloro-3-methylphenol was converted to the title compound by a method similar to that described in Example 2: mp 207.5-209.3 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.77 (s, 1H), 7.23 (s, 1H), 6.90 (s, 1H), 5.65 (q, 1H, J = 6.8Hz), 2.37 (s, 3H). FABLRMS m / z 292 (M + H). FABHRMS m / z 299.0287 (M + Li, calculated 299.0274). Analytical Calcd for C 12 H 8 ClF 3 O 3 : C, 49.25; H, 2.76; Cl, 12.11. Found: C, 49.37; H, 2. 82; Cl, 12.17. Example 7 6- (4-methoxyphenoxy) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 4- (4-methoxyphenyl) phenol was converted to the title compound by a method similar to that described in Example 2: mp 181.7-182.9 ° C. 1 H NMR (acetone -d 6/300 MHz) 7.87 ( s, 1H), 7.11 (m, 1H), 7.02 (m, 2H), 6.98 (m, 4H), 5.81 (q, 1H, J = 7.0Hz ), 3.80 (s, 3 H). FABLRMS m / z 365 (MH). FABHRMS m / z 367.0809 (M + H, calculated 367.0793). Analytical Calcd for C 18 H 13 F 3 O 5 : C, 59.02; H, 3.58. Found: C, 59.10; H, 3.61. Example 8 6-chloro-7- (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of 4-tert-butylsalicylaldehyde Trifluoroacetic acid (2.4 L) was placed in a 5-liter three-necked round flask equipped with an overhead mechanical stirrer and condenser. A mixture of 3-tert-butylphenol (412 g, 2.8 mmol) and HMTA (424 g, 3.0 mmol) was added in portions to cause exotherm. The temperature was kept at 80 ° C. or lower while cooling. The reaction was heated at 80 ° C. for one hour, then cooled and water (2 L) was added. After 0.5 h, additional water (4 L) was added and the mixture was extracted with ethyl acetate (6 L). This organic extract was washed with water and brine. The resulting organic phase was divided into 2 L volumes and each was diluted with water (1 L) and solid NaHCO 3 was added until the mixture was neutralized. The organic phases are separated, combined, dried over MgSO 4 , filtered and concentrated in vacuo to give an oil. This oil was distilled (0.8 mm) at 95 ° C. to give the required salicylate as an oil of sufficient purity for use without further purification (272.9 g, 56%). Step 2. Preparation of ethyl 7- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate 4-tert-butylsalicylaldehyde (step 1) (100.0 g, 0.56 mole), dimedylformamide (110 ml) and potassium carbonate salt (79.9 g, 0.58 mole) were added to a 1 liter three-neck flask. The temperature of was heated to 40 ° C. Ethyl 4,4,4-trifluorocrotonate (118.0 g, 0.70 mole) in dimethylformamide (110 ml) was added and the mixture was heated to 60 ° C and at some point the reaction temperature was raised to 70 ° C. The reaction was cooled to 60 ° C. and kept at 60 ° C. (additionally heated) for 8.5 hours and cooled to room temperature. Ethyl acetate (600 ml) and 3N HCl (600 ml) were added, mixed and phase separated. The aqueous phase was extracted with ethyl acetate and the organic phases were combined. The combined organic phases were washed with brine-water (1: 1), brine, dried over MgSO 4 , filtered and concentrated in vacuo to give a semisolid. Hexane (600 ml) was added with mixing and the mixture was filtered. The filtrate was washed with brine, dried over MgSO 4 , filtered and concentrated in vacuo to give a solid. This solid was dissolved in hot ethanol (600 ml). Water (190 ml) was added to induce crystallization. The mixture was filtered and the product dried to give the required ester as a crystalline solid (131.3 g, 71%): mp 91.0-94.9 ° C. This material was of a suitable purity for use in subsequent steps without further purification. Step 3. Preparation of ethyl 6-chloro-7- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate In a 1 liter three-necked flask equipped with a mechanical stirrer and a gas inlet tube was added ester (step 2) (100.0 g, 0.3 mole) and acetic acid (300 ml). While cooling this reaction mixture (water electrolyzer), chlorine gas (37.6g, 0.3mole) was added and the temperature was raised to 48 degreeC. After stirring for 2 hours, the reaction was cooled to 15 ° C. in an ice water electrolyzer. A portion of zinc powder (19.5 g, 0.3 mole) was added to raise the temperature to 72 ° C. After cooling to room temperature, additional zinc powder (5.0 g, 0.08 mole) was added and the mixture was stirred for another 0.5 h. This crude mixture was filtered through diatomaceous earth and concentrated in vacuo to afford an oil. This oil was dissolved in ethyl acetate (700 ml) and washed with brine-water (1: 1, 1 L) and brine (0.5 L). The resulting aqueous phase was extracted with ethyl acetate (700 ml). This ethyl acetate phase was washed with brine-water (1: 1, 1L) and brine (0.5L). The combined organic phases were dried over MgSO 4 , filtered and concentrated in vacuo to afford the title compound as a yellow oil (116 g, 106%). This material, including some incorporated ethyl acetate, was of purity suitable for use in subsequent steps without further purification. Step 4. Preparation of 6-Chloro-7- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Aqueous sodium hydroxide (2.5 N, 240 mL, 0.6 mole) was added to a solution of ester (step 3) (116 g, 0.3 mole) in methanol (500 mL) and tetrahydrofuran (500 mL) in a 1 liter flask. After stirring overnight, the pH of the solution was adjusted to 1 with concentrated hydrochloric acid and the solution was extracted with ethyl acetate. This ethyl acetate phase was dried over MgSO 4 , filtered and concentrated in vacuo to give a solid. This solid was dissolved in hot ethanol (500 mL). Water (500 mL) was added and cooled to room temperature, crystals formed and collected by vacuum filtration. The crystals were washed with ethanol-water (3: 7, 3x200 mL) and dried to give the title acid as crystalline solid (91.6 g, 91%): mp 194.9-196.5 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.86 (s , 1H), 7.52 (s, 1H), 7.12 (s, 1H), 5.83 (q, 1H, J = 7.1Hz), 1.48 (s, 9H) . Analytical Calcd for C 15 H 14 ClF 3 O 3 : C, 53.83; H, 4. 22; Cl, 10.59. Found: C, 53.92; H, 4. 24; Cl, 10.50. Example 9 6- (3-chloro-4-methoxyphenoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 6- (4-methoxyphenoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid in a chlorine solution (3.5 mL of 0.24 mole solution, 0.84 mmol) in stirred acetic acid ( 0.31 g, 0.85 mmol) was added (Example 7). After 1 hour, additional chlorine solution (1.5 mL of 0.24 mole solution, 0.36 mmol) in acetic acid was added. After an additional 3 hours, additional chlorine acetate (0.25 mole solution 0.25 mL, 0.06 mmol) was added. After 2.5 hours, the reaction was cooled in an aqueous 10% sodium bisulfite solution and the resulting mixture was extracted with ethyl acetate. The organic phase was washed with water, brine, dried over MgSO 4 , filtered and concentrated in vacuo to give a yellow oil. This oil was dissolved in a minimum amount of hexane to induce crystallization. The mixture was vacuum filtered to give the title compound as yellow crystals (0.18 g, 53%): mp 205-207 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.89 (s , 1H), 6.97-7.18 (m, 6H), 5.83 (q, 1H, J = 7.0Hz), 3.90 (s, 3H). FABLRMS m / z 400 (M < + >). FABHRMS m / z 399.0249 (M−H, calcd 399.0247). Analytical Calcd for C 18 H 12 ClF 3 O 5 : C, 53.95; H, 3.02; Cl, 8.85. Found: C, 53.78; H, 3.08; Cl, 8.98. Example 10 2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl 2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate The ester was prepared from salicylic aldehyde by a method similar to that described in Example 1, Step 1: bp 107 ° C. 2 mm. 1 HNMR (acetone -d 6 / 300MHz) 7.89 (s , 1H), 7.52-7.38 (m, 2H), 7.09 (dt, 1J = 1.0. 7.7Hz), 7.03 (d, 1H, J = 8.3Hz), 5.84 (q, 1 H, J = 7.3 Hz). 4.39-4.23 (m, 2 H), 1.33 (t, 3 H, J = 7.0 Hz). FABLRMS m / z 273 (M + H). ESHRMS (m / z 273.0720 (M + H, calculated 273.0739). Step 2. Preparation of 2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid The acid was prepared from ethyl ester (step 1) by a similar method as described in Example 1, step 2: mp 152.2-153.3 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.89 (s , 1H), 7.39-7.49 (m, 2H), 7.11-7.01 (m, 2H), 5.81 (q, HF, 1H, J = 7.2Hz). FABHRMS m / z 245.0422 (M + H, calculated 245.0426). Analytical Calcd for C 11 H 7 F 3 O 3 : C, 54.11; H, 2.89. Found: C, 54.22; H, 2.97. Example 11 6,8-dichloro-7-methyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of 3,5-dichloro-4-methylsalicylaldehyde 2,4-Dichloro-3-methylphenol (25.0 g, 141.2 mmol) was added to methanesulfonic acid (100 mL). While stirring, hexamethylenetetramine (HMTA) (39.8 g, 282.4 mmol) and additional methanesulfonic acid (100 mL) were added in portions to cause the reaction to start and exotherm while bubbling during that time. The resulting mixture was heated to 100 ° C. for 3 hours. This crude ocher suspension was cooled to 50 ° C. and poured into a mechanically stirred ice water (2 L) mixture. A yellow precipitate formed and was collected by vacuum filtration. This solid was purified by flash chromatography (silica, hexane-methylene chloride, 9:10) to give salicylic aldehyde as a pale yellow powder of purity suitable for use without further purification (6.17 g, 21%; mp 94.0). -95.1 ° C). Step 2. Preparation of ethyl 6,8-dichloro-7-methyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate 3,5-dichloro-4-methylsalicylaldehyde (step 1) (5.94 g, 29.0 mmol) and ethyl 4,4,4-trifluorocrotonate (7.67 g, 45.6 mmol) dissolved in anhydrous DMSO (10 mL) ) Was treated with triethylamine (5.88 g, 58.1 mmol). The reaction was stirred at 85 ° C. for 49 hours, then cooled in ice and filtered to yield an orange solid. This solid was dissolved in ethyl acetate (100 mL), washed with 3N HCl (2 × 50 mL), saturated NaHCO 3 and brine, dried over MgSO 4 and concentrated in vacuo to yield a yellow solid (8.63 g, 84%). : mp 117.1-119.5 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.63 (s , 1H), 7.17 (s, 1H), 5.80 (q, 1H, J = 6.6Hz), 4.33 (m, 2H), 2.48 (s, 3H) , 1.35 (t, 3H, J = 7.1 Hz). Step 3. Preparation of 6,8-dichloro-7-methyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid The ester from step 2 (8.39 g, 23.6 mmol) was dissolved in THF (30 mL) and ethanol (20 mL), treated with 2.5N sodium hydroxide (20 mL, 50 mmol) and stirred at rt for 3.5 h. The reaction mixture was concentrated in vacuo, acidified with 3N HCl, filtered and recrystallized from ethanol / water to give a yellow solid (6.0 g, 78%): mp 229.9-230.9 ° C. 1 H NMR (acetone -d 6/300 MHz) 7.90 ( s, 1H), 7.58 (s, 1H), 6.00 (q, 1H, J = 6.8Hz), 2.50 (s, 3H). FABHRMS m / z 325 (M−H). FABHRMS m / z 324.9636 (MH, calculated 324.9646). Analytical Calcd for C 12 H 7 Cl 2 F 3 O 3 : C, 44.07; H, 2. 16; Cl, 21.68. Found: C, 44.06; H, 2. 21; Cl, 21.74. Example 12 7- (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid Ethyl 7- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 8, Step 2) is described in Step 2 of Example 1 Hydrolyzed to carboxylic acid according to a similar method as that: mp 165.6-166.8 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.86 (s , 1H), 7.38 (d, 1H, J = 8.1Hz), 7.15 (dd, 1H, J = 1.8Hz, and J = 7.8Hz). 7.05 (bs, 1 H), 5.79 (q HF , 1 H, J = 7.2 Hz), 1.32 (s, 9H). FABHRMS m / z 301.1033 (M + H, calculated 301.1051). Analytical Calcd for C 15 H 15 F 3 O 3 : C, 60.00; H, 5.04. Found: C, 59.80; H, 5.10. Example 13 6-Bromo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 5-Bromosalicylaldehyde was converted to the title compound by a method similar to that described in Example 1: mp 189.6-190.9 ° C. 1 H NMR (acetone -d 6/300 MHz) 7.89 ( s, 1H), 7.70 (d, 1H, J = 2.1Hz), 7.55 (dd, 1H, J = 2.4Hz, and J = 8.7Hz). 7.02 (d, 1H, J = 8.7 Hz), 5.86 (q HF , 1H, J = 7.2 Hz). FABHRMS m / z 322.9519 (M + H, calculated 322.9531). Analytical Calcd for C 11 H 6 BrF 3 O 3 : C, 40.90; H, 1.87; Br, 24.73. Found: C, 40.87; H, 1.92; Br, 24.80. Example 14 8-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 2-Chlorophenol was converted to the title compound by a method similar to that described in Example 2: mp 224.5-225.6 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.91 (s , 1H), 7.49 (m, 2H), 7.11 (t, 1H, J = 7.8Hz), 5.96 (q HF, 1H, J = 7.2 Hz). FABHRMS m / z 279.0027 (M + H, calculated 279.0036). Analytical Calcd for C 11 H 6 ClF 3 O 3 : C, 47.42; H, 2.17. Found: C, 47.33; H, 2.17. Example 15 8-Bromo-6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 2-Bromo-4-chlorosalicylaldehyde was converted to the title compound by a method similar to that described in Example 1: mp 227.8-228.9 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.90 (s , 1H), 7.65 (dd, 2H, J = 2.4 and J = 28.8Hz), 6.00 (q HF, 1H, J = 7.2Hz). FABHRMS m / z 356.9134 (M + H, calculated 356.9141). Analytical calcd. For C 11 H 6 BrClF 3 O 3 : C, 36.96; H, 1.41. Found: C, 37.05; H, 1.33. Example 16 6-trifluoromethoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 5- (trifluoromethoxy) salicyaldehyde was converted to the title compound by a method similar to that described in Example 1: mp 118.4-119.5 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.95 (s , 1H), 7.54 (d, 1H, J = 2.1Hz), 7.39 (dd, 1H, J = 2.4Hz, and J = 9.0Hz), 7.02 ( d, 1H, J = 9.0 Hz), 5.88 (q HF , 1H, J = 7.2 Hz). FABHRMS m / z 329.0228 (M + H, calculated 329.0249). Analytical Calcd for C 12 H 6 F 6 O 4 : C, 43.92; H, 1.84. Found: C, 43.84; H, 1.87. Example 17 8-Fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 3-Fluorsalicylaldehyde was converted to the title compound by a method similar to that described in Example 1: mp 197.7-210.1 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.94 (s , 1H), 7.30 (m, 2H), 7.11 (m, 1H), 5.93 (q HF, 1H, J = 7.2Hz). FABHRMS m / z 263.0341 (M + H, calculated for C 11 H 6 F 4 O 3 263.0331). Analytical calcd. For C 11 H 6 F 4 O 3 : C, 50.40; H, 2.31. Found: C, 50.48; H, 2.25. Example 18 5,7-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 4,6-Dichlorosalicylaldehyde was converted to the title compound by a method similar to that described in Example 1: mp 190.1-191.2 ° C. 1 H NMR (acetone -d 6 / 300MHz) 8.01 (s , 1H), 7.3 (bs, 1H), 7.16 (bs, 1H), 5.94 (q HF, 1H, J = 7.2Hz). FABHRMS m / z 312.9636 (M + H, calculated 312.9646). Analytical Calcd for C 11 H 6 Cl 2 F 3 O 3 : C, 42.20; H, 1.61. Found: C, 42.27; H, 1.56. Example 19 7,8-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 3,4-Dichlorophenol was converted to the title compound by a method similar to that described in Example 2: mp 219.5-220.5 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.94 (s , 1H), 7.51 (d, 1H J = 8.4Hz), 7.34 (d, 1H, J = 8.4Hz), 6.02 (q HF, 1H, J = 7.2 Hz). FABHRMS m / z 318.9729 (M + Li, CI 11 H 6 Cl 2 F 3 O 3 calc. 318.9728). Analytical Calcd for C 11 H 6 Cl 2 F 3 O 3 : C, 42.20; H, 1.61. Found: C, 42.15; H, 1.68. Example 20 7-isopropyloxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 4- (1-methylethyloxy) salicylaldehyde was prepared by alkylating 3,4-dihydroxybenzaldehyde: This salicylicaldehyde was converted to the title compound by a similar method as described in Example 1: mp 161-163 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.73 (s, 1 H), 7.21 (d, 1 H, J = 8.5 Hz), 6.57 (dd, 1H, J = 8.5, 2.2 Hz). FABHRMS m / z 301.0688 (MH + , requires C 11 H 12 F 3 O 4 301.0687). Analytical Calcd for C 11 H 13 F 3 O 4 : C, 55.63; H, 4.34. Found: C, 55.72; H, 4.34. Example 21 8-phenyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 2-phenylphenol was converted to the title compound by a method similar to that described in Example 2: mp 171.6-175.0 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.95 (s , 1H), 7.46 (m, 7H), 7.18 (t, 1H, J = 7.5Hz) 5.81 (q HF, 1H, J = 7.2Hz). FABHRMS m / z 327.0816 (M + Li, 327.0820). Analytical Calcd for C 17 H 11 F 3 O 3 : C, 63.76; H, 3.46. Found: C, 63.52; H, 3.55. Example 22 7,8-dimethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 2,3-dimethylphenol was converted to the title compound by a method similar to that described in Example 2: mp 245.2-247.3 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.83 (s , 1H), 7.17 (d, 1H, J = 7.8Hz), 6.89 (d, 1H, J = 7.8Hz) 5.82 (q HF, 1H, J = 7.2 Hz). 2.30 (s, 3 H), 2.17 (s, 3 H). Anal calcd. For C 13 H 11 F 3 O 3 + 1.56% H 2 O: C, 56.46; H, 4.18. Found: C, 56.46; H, 4.15. Example 23 6,8-bis (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 3,5-di-tert-butylsalicylaldehyde was converted to the title compound by a method similar to that described in Example 1: mp 171.6-175.0 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.65 (s , 1H), 7.34 (d, 1H, J = 2.4Hz), 7.15 (d, 1H, J = 2.4Hz), 6.02 (q HF, 1H, J = 7.2 Hz). FABHRMS m / z 363.1743 (M + Li, 363.1759). Analytical Calcd for C 19 H 23 BrF 3 O 3 : C, 64.03; H, 6.50. Found: C, 64.13; H, 6.49. Example 24 6-iodo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of 2-hydroxy-5-iodobenzyl alcohol The solution of 5-iodosalicylic acid (25.0 g, 94.6 mmol) in tetrahydrofuran (500 mL) was cooled to 0 ° C. With vigorous stirring, borane-methyl sulfide complex (15.1 mL of 10M solution, 151.0 mmol) was added dropwise over 0.25 hours. The solution was warmed to room temperature and then heated to reflux for 4 hours. A white precipitate formed during reflux. The solution was cooled to room temperature and 10% aqueous hydrochloric acid (100 mL) was added over 15 minutes and stirred at room temperature for 2 hours. The dissolved precipitate and solvent were concentrated in vacuo to a volume of approximately 200 mL. The solution was poured into ethyl acetate (300 mL) and washed with water (2 x 200 mL), saturated sodium bicarbonate (2 x 200 mL), saturated sodium bicarbonate (2 x 200 mL), and saturated ammonium chloride (2 x 200 mL). . The organic phase was dried over sulfuric sodium and concentrated in vacuo. 2-hydroxy-5-yodobenzyl alcohol was isolated from hexane as a white solid (21.3 g, 85.2 mmol) (90% yield): mp 105-110 ° C. 1 H NMR (CDCl 3/300 MHz) 8.21 (s, 1H), 7.30-7.33 (M, 2H), 6.57 (d, 1H, J = 8.3Hz), 4.97 (bs, 1H), 4.62 (s, 2H ). EIHRMS m / z = 249.9492 (M < + >, 249.9491). Step 2. Preparation of 2-hydroxy-5-iodobenzaldehyde To a stirred solution of 2-hydroxy-5-iodobenzyl alcohol (43.5 g, 174.0 mmol) in acetone (700 mL) was added 85% activated manganese (IV) oxide (5 microns, 50 g, 494.0 mmol) and the solution was added 16 Stir at room temperature for hours. Manganese oxide was filtered off through diatomaceous earth and the filtrate was concentrated in vacuo. This product was purified by flash silica chromatography (0-20% ethyl acetate in hexanes). 2-hydroxy-5-iodobenzaldehyde was obtained as a greenish yellow solid (24.3 g, 58%). A small amount of 2-hydroxy-5-iodobenzaldehyde was recrystallized from methanol / water to make an analytical sample and the rest of the compound was used without further purification: mp 99-101 ° C. 1 H NMR (CDCl 3 / 300MHz ) 9.83 (s, 1H), 7.79 (d, 1H, J = 2.2Hz), 7.77 (dd, 1H, J = 8.7Hz, J = 2.2Hz), 6.81 (d, 1H , J = 8.7 Hz), ESHRMS 246.9229 (MH, calculated 246.9256). Step 3. Preparation of ethyl 6-iodo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylate Combine a mixture of 5-iodosalicylaldehyde (16.2g, 65.3mmol), ethyl 4,4,4-trifluorocrotonate (22.4g, 133mmol) and triethylamine (50ml, 395mmol) and 8 hours at 70 ° C Stirred for and then heated to reflux for 48 hours. This solution was poured into ethyl acetate (300 mL) and washed with 1N hydrochloric acid (3 x 200 mL). The aqueous phases were combined and extracted with ethyl acetate (1 × 100 mL). The combined ethyl acetate extracts were washed with saturated ammonium chloride (2 x 200 mL), dried over magnesium sulfate and concentrated in vacuo to yield a dark red oil. This oil was purified by flash chromatography using ethyl acetate-hexane (3: 7) to yield a red oil. This oil was recrystallized from hexanes to give the title compound as light red crystals (8.3 g, 31%): mp 105-106 <0> C. 1 H NMR (CDCl 3 / 300MHz ) 7.63 (s, 1H), 7.58 (dd, 2H, J = 8.6Hz, J = 2.1Hz), 7.54 (d, 1H, J = 2.1Hz), 6.77 (d, 1H , J = 8.6 Hz), 5.70 (q, 1H, J = 6.7 Hz), 4.20-4.38 (m, 2H), 1.35 (t, 3H, J = 7.2 Hz). ESHRMS 415.9926 (M < + >-NH 4 + , calcd 396.9746). Step 4. Preparation of 6-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Hydrolysis of the ester (step 3) using a method similar to Example 1, step 2 yielded the carboxylic acid: mp 168-170 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.57 (s, 1 H), 7.70 (d, 1 H, J = 2.2 Hz), 7.64 (dd, 1H, J = 8.5 Hz, J = 2.2 Hz), 7.64 (dd, 1H, J = 8.5 Hz, J = 2.2 Hz, 6.79 (d, 1H, J = 8.5 Hz), 5.78 (q, 1H, J = 7.0 Hz). ESHRMS m / z 368.9222 (calculated for MH 368.9235). Analytical calcd. For C 11 H 6 F 3 IO 3 : C, 35.70; H, 1.63. Example 25 7- (1-methylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 3- (1-methylethyl) phenol was converted to the title compound by a method similar to that described in Example 2: mp 158.3-159.7 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.86 (s , 1H), 7.37 (d, 1H, J = 7.8Hz), 7.00 (d, 1H, J = 7.8Hz), 6.91 (s, 1H), 5.78 (q, 1H, J = 6.9 Hz), 2.93 (m, 1H), 1.24 (d, 6H, J = 6.9 Hz). FABLRMS m / z 287 (M + H). Analytical Calcd for C 14 H 13 F 3 O 3 : C, 58.74; H, 4.58. Found: C, 57.37; H, 4.49. Example 26 7-phenyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 3-phenylphenol was converted to the title compound by a method similar to that described in Example 2: mp 209.4-211.7 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.94 (s , 1H), 7.74 (m, 2H), 7.47 (m, 5H), 7.33 (s, 1H), 5.86 (q, 1H, J = 7.2Hz) . FABLRMS m / z 321 (M + H). Analytical Calcd for C 17 H 11 F 3 O 3 : C, 63.76; H, 3.46. Found: C, 64.17; H, 3.61. Example 27 6-chloro-7-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 4-chloro-3-ethylphenol was converted to the title compound by a method similar to that described in Example 2: mp 170.7-172.1 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.78 (s, 1H), 7.26 (s, 1H), 6.90 (s, 1H), 5.67 (q, 1H, J = 6.9Hz). 2.73 (q, 2H, J = 7.8 Hz). 1.24 (t, 3H, J = 7.8 Hz). FABLRMS m / z 307 (M + H). Analytical Calcd for C 13 H 10 F 3 O 3 : C, 50.92; H, 3.29. Found: C, 51.00; H, 3.33. Example 28 8-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 2-ethylphenol was converted to the title compound by a method similar to that described in Example 2: mp 185.4-186.8 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.85 (s , 1H), 7.28 (d, 2H, J = 7.5Hz), 7.00 (t, 1H, J = 7.5Hz). 5.84 (q, 1 H, J = 7.2 Hz). 2.65 (m, 2H), 1.18 (t, 3H, J = 7.5 Hz). FABLRMS m / z 273 (M + H). Analytical Calcd for C 13 H 11 F 3 O 3 : C, 57.36; H, 4.07. Found: C, 57.15; H, 4.11. Example 29 6-chloro-8-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 8-ethyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid (Example 28) (0.68 g, 2.5 mmol) was dissolved in trimethylphosphate (5 mL) and sulfyl at 0 ° C. Treated with chloride (0.35 g, 2.62 mmol). After stirring for 45 minutes at 0 ° C. and 1 hour at room temperature, the reaction was diluted with cold water (15 mL). The resulting oily mixture was extracted with hexane-ethyl acetate. The organic phase was washed with brine, dried and concentrated in vacuo to give the title compound as a solid (0.9 g, 117%): mp 197.2-199.1 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.86 (s , 1H), 7.38 (d, 1H, J = 2.7Hz), 7.30 (d, 1H, J = 2.4Hz). 5.88 (q, 1 H, J = 7.2 Hz). 2.65 (m, 2H), 1.19 (t, 3H, J = 7.5 Hz). FABLRMS m / z 307 (M + H). Analytical Calcd for C 13 H 10 ClF 3 O 3 : C, 50.92; H, 3.29. Found: C, 51.00; H, 3.23. Example 30 6-chloro-7-phenyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 7-phenyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid (Example 26) was converted to the title compound by a method similar to that described in Example 29: mp 185.3 -187.8 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.94 (s , 1H), 7.68 (s, 1H), 7.47 (m, 5H), 7.06 (s, 1H), 5.87 (q, 1H, J = 6.9Hz) . FABLRMS m / z 355 (M + H). Analytical Calcd for C 17 H 10 ClF 3 O 3 : C, 57.56; H, 2. 84. Found: C, 58.27; H, 3.11. Example 31 6,7-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 3,4-dichlorophenol was converted to the title compound by a method similar to that described in Example 2: mp 196.1-198.3 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.90 (s , 1H), 7.74 (s, 1H), 7.30 (s, 1H), 5.88 (q, 1H, J = 6.9Hz). FABLRMS m / z 314 (M + H). Analytical Calcd for C 11 H 5 Cl 2 F 3 O 3 : C, 42.20; H, 1.61. Found: C, 42.31; H, 1.65. Example 32 6,8-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 3,5-Dichlorosalicylaldehyde was converted to the title compound by a method similar to that described in Example 11, steps 2 and 3: mp 212.8-216.8 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.77 (s, 1H), 7.41 (d, 1H, J = 2.4Hz), 7.18 (d, 1H, J = 2.2Hz), 5.82 (q, 1H, J = 6.7Hz ). FABLRMS m / z 311 (MH). Analytical calcd. For C 11 H 5 F 3 Cl 2 O 3 : C, 42.20; H, 1.61. Found: C, 42.50; H, 1.71. Example 33 6,8-dibromo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 3,5-Dibromosalylsilaldehyde was converted to the title compound by a method similar to that described in Example 1: mp 225-226 ° C. 1 H NMR (CD 3 OD / 300MHz) 7.76 (s, 1H), 7.74 (d, 1H, J = 2.2 Hz), 7.55 (d, 1H, J = 2.2 Hz), 5.91 (q HF , 1H, J = 7.2 Hz). FABHRMS m / z 400.8648 (M + H + , 400.8636). Analytical Calcd for C 11 H 5 Br 2 F 3 O 3 : C, 32.87; H, 1.25. Found: C, 33.47; H, 1.38. Example 34 6,8-dimethoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 4,6-Dimethoxysalicylaldehyde was converted to the title compound by a method similar to that described in Example 1: mp 215-217 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.95 (s, 1 H), 6.18-6.20 (m, 2 H), 5.65 (q HF , 1 H, J = 7.2 Hz). 3.87 (s, 1 H), 3.81 (s, 1 H). FABHRMS m / z 303.0497 (M−H + , calculated 303.0380). Analytical Calcd for C 13 H 11 F 3 O 5 : C, 51.33; H, 3.64. Found: C, 51.19; H, 3.71. Example 35 Ethyl 6-amino-2-trifluoromethyl-2H-1-benzopyran-3-carboxylate Step 1. Preparation of ethyl 6-nitro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate A mixture of 5-nitrosalicylaldehyde (4.80 g, 28.7 mmol) and ethyl 4,4,4-trifluorocrotonate (6.6 g, 39.4 mole) in anhydrous DMF was warmed to 60 ° C. and anhydrous K 2 CO 3 (3.90 g, 28.9 mole). This solution was kept at 60 ° C. for 20 hours, cooled to room temperature, diluted with water and extracted with ethyl acetate. This organic extract was washed with brine, dried over anhydrous MgSO 4, filtered and concentrated in vacuo to yield an oil. This oil was dissolved in diethyl ether (5 mL). Hexane was added until the solution became cloudy. It was left at room temperature overnight to obtain an ester as yellow crystals (0.856 g, 7% yield). This material was of sufficient purity for use in subsequent steps without further purification. 1 H NMR (CDCl 3 / 300MHz ) 8.15-8.19 (m, 2H), 7.74 (s, 1H), 7.09 (d, 1H, J = 8.9Hz), 5.81 (d, 1H, J = 5.8Hz), 4.29 -4.39 (m, 2 H). 1.35 (t, 3H, J = 6.0 Hz). Step 2. Preparation of ethyl 6-amino-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate Ester (step 1) (0.345 g, 1.08 mmol) was stirred in ethanol (10.0 mL) for 1 hour using 10% platinum on activated carbon (15 mg) under 1 atmosphere of pressure, hydrogen. The catalyst was filtered off and the solvent removed in vacuo to give the title compound as an orange-yellow solid (0.298 g, 95%): mp 111-115 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.69 (s, 1 H), 6.69-6.74 (M, 3 H), 5.65 (q HF , 1 H, J = 7.2 Hz). 4.26-4.37 (m, 2 H), 1.34 (t, 3 H, J = 7 Hz). FABHRMS m / z 288.0860 (M + H + , requires C 13 H 13 F 3 NO 3 288.0847). Analytical Calcd for C 13 H 12 F 3 NO 3 : C, 54.36; H, 4.21. Found: C, 54.46; H, 4.83; N, 4.83. Example 36 6-amino-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid Ethyl 6-amino-2- (nitrofluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 35, Step 2) was prepared by a similar method as described in Example 1 Hydrolysis): mp 216-133 ° C. 1 H NMR (CD 3 OD / 300 MHz) 6.81-6.90 (m, 3H), 5.66 (q HF , 1H, J = 7.2 Hz). FABHRMS m / z 260.0535 (M + H + , requires C 11 H 9 F 3 NO 5 260.0535). Example 37 6-nitro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid Ethyl 6-nitro-2- (nitrofluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 35, Step 1) was prepared by a similar method as described in Example 1 Hydrolysis): mp 187-189 ° C. 1 H NMR (CD 3 OD / 300MHz) 8.34 (d, 1H, J = 2.6 Hz), 8.27 (dd, 1H, J = 8.7, 2.6 Hz), 7.90 (s, 1H), 7.09 (s, 1H, J = 8.7 Hz), 5.81 (q HF , 1H, J = 7.2 Hz). EIHRMS m / z 289.0177 calculated 289.0198). Analytical Calcd for C 11 H 6 F 3 NO 5 : C, 45.69; H, 2.09; N, 4.84. Found: C, 45.71; H, 2.08; N, 4.75. Example 38 6-chloro-8-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 4-chloro-2-methylphenol was converted to the title compound by a method similar to that described in Example 2: mp 231.9-233.2 ° C. 1 H NMR (CDCl 3 / 300MHz) 7.76 (s, 1H), 7.19 (d, 1H, J = 1.8Hz), 7.09 (d, 1H, J = 2.4Hz), 5.72 (q, 1H, J = 6.9Hz ), 2.24 (s, 3 H). 19 F NMR (CDCl 3 / 282MHz ) -79.2 (d, J = 6.5Hz). FABLRMS m / z 299 (M + Li). FABHRMS m / z 293.0196 (M + H, calculated 293.0192). Analytical Calcd for C 12 H 6 ClF 3 O 3 : C, 49.25; H, 2.76. Found: C, 49.37; H, 2.86. Example 39 8-chloro-6-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 2-Chloro-4-methylphenol was converted to the title compound by a method similar to that described in Example 2: mp 226.4-227.4 ° C. 1 H NMR (CDCl 3 / 300MHz) 7.79 (s, 1H), 7.23 (d, 1H, J = 1.4Hz), 6.97 (d, 1H, J = 1.4Hz), 6.97 (d, 1H, J = 1.4Hz ), 5.77 (q, 1H, J = 6.8 Hz). 2.29 (s, 3 H). 19 F NMR (CDCl 3 / 282MHz ) -79.1 (d, J = 7.3Hz). FABLRMS m / z 291 (MH). EIHRMS m / z 292.0118 (M < + >, C 12 H 6 ClF 3 O 3 calculated 292.0114) Example 40 8-chloro-6-methoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 2-Chloro-6-methoxyphenol was converted to the title compound by a method similar to that described in Example 2: mp 204.5-206.9 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.78 (s, 1H), 6.98 (d, 1H, J = 2.8Hz), 6.71 (d, 1H, J = 2.8Hz), 5.74 (q, 1H, J = 6.9Hz ), 3.79 (s, 3 H). FABLRMS m / z 326 (M + NH 4 ). EIHRMS m / z 308.0053 (M < + >, 308.0063). Analytical Calcd for C 12 H 8 ClF 3 O 4 : C, 46.60; H, 2.68. Found: C, 46.60; H, 2.68. Example 41 6,8-difluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 2,4-difluorophenol was converted to the title compound by a method similar to that described in Example 2: mp 207-211 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.63 (s, 1H), 6.89-6.72 (m, 2H), 5.69 Analysis for (q, 1H, J = 6.7Hz), C 11 H 3 F 5 O 5 Calculated: C, 47.16; H, 1.80. Found: C, 47.28; H, 1.87. Example 42 6-Bromo-8-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 4-Bromo-2-chlorophenol was converted to the title compound by a method similar to that described in Example 2: mp 220.7-221.7 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.58 (s, 1H), 7.44 (d, 1H, J = 2.2Hz), 7.22 (d, 1H, J = 2.2Hz), 5.74 (q, 1H, J = 6.8Hz ), Anal. Calcd. For C 11 H 5 O 3 F 3 BrCl: C, 36.96; H, 1.41. Found: C, 37.03; H, 1.44. Example 43 8-Bromo-6-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 2-Bromo-4-fluorophenol was converted to the title compound by a method similar to that described in Example 2: mp> 300 ° C. 1 H NMR (CDCl 3 ) 7.58 (s, 1H), 7.22 (dd, 1H, J = 6.3, 3 Hz), 6.88 (dd, 1H, J = 6.1, 3.1 Hz), 5.72 (q, 1H, J = 6.7 Hz), C 11 H 5 0 3 F 4 Br: C, 38.74 for analytical calculations. H, 1.48. Found: C, 38.82; H, 1.56. Example 44 8-Bromo-6-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 2-Bromo-4-methylphenol was converted to the title compound by a method similar to that described in Example 2: mp 237-238 ° C. 1 H NMR (CDCl 3 ) 7.59 (s, 1 H), 7.27 (m, 1 H), 6.91 (d, 1 H, J = 1.4 Hz), 5.69 (q, 1H, J = 6.9 Hz), 2.20 (s, 3H ). Analytical Calcd for C 12 H 8 O 3 F 3 Br: C, 42.76; H, 2.39. Found: C, 43.34; H, 2.56. Example 45 8-Bromo-5-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 2-Bromo-5-fluorophenol was converted to the title compound by a method similar to that described in Example 2: mp 221.7-223.3 ° C. 1 H NMR (CDCl 3 ) 7.81 (s, 1H), 7.38 (dd, 1H, J = 7.3, 5.8 Hz), 6.58 (t, 1H, J = 8.9 Hz), 5.71 (q, 1H, J = 6.7 Hz ). Analytical Calcd for C 11 H 5 0 3 F 4 Br: C, 38.74; H, 1.48. Found: C, 38.70; H, 1.54. Example 46 6-chloro-8-fluuro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 4-Chloro-2-fluorophenol was converted to the title compound by a method similar to that described in Example 2: mp 190.8-193.0 ° C. 1 H NMR (CDCl 3 ) 7.77 (s, 1 H), 7.19 (d of d, 1 H, J = 2.2, 9.7 Hz), 7.07 (t, 1H, J = 1.8 Hz), 5.76 (q, 1H, J = 6.7 Hz). FABLRMS m / z 295 (MH). EIHRMS m / z 295.9876 (M + found 295.9863). Analytical Calcd for C 11 H 5 ClF 4 O 3 : C, 44.54; H, 1.70. Found: C, 44.36; H, 1.85. Example 47 6-Bromo-8-methoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 4-Bromo-2-methoxysalicylaldehyde was converted to the title compound by a method similar to that described in Example 1: mp 244 ° C. 1 H NMR (CD 3 OD / 300MHz) 7.71 (s, 1H), 7.18 (d, 1H, J = 2.2Hz), 7.11 (d, 1H, J = 2.2Hz), 5.77 (q HF, 1H, J = 7.2 Hz). 3.84 (s, 3 H). FABLRMS m / z 351 (mH). Analytical Calcd for C 12 H 8 BrF 3 O 5 : C, 40.82; H, 2.28. Found: C, 40.83; H, 2.30. Example 48 7- (N, N-diethylamino) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 4- (N, N-diethylamino) salicyaldehyde was converted to the title compound by a method similar to that described in Example 1: mp 214.4-215.4 ° C. 1 H NMR (CD 3 OD / 300MHz) 7.67 (s, 1H), 7.06 (d, 1H, J = 8.6Hz), 6.34 (dd, 1H, J = 8.6, 2.3Hz), 5.60 (q HF, 1H, J = 7.2 Hz). 3.38 (q, 4H J = 7.1 Hz). 1.16 (t, 6H, J = 7.1 Hz). ESLRMS m / z 316 (M + H). FABLRMS m / z 361.1145 (M + H +, calc. 316.1161). Analytical Calcd for C 15 H 16 F 3 NO 3 : C, 57.14; H, 5.11; N, 4.44. Found: C, 57.14; H, 5.08. N, 4.44. Example 49 6-[[(phenylmethyl) amino] sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl 6-chlorosulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylate Chlorosulfonic acid (50.0 mL) was cooled to 15 ° C. and ethyl 2-trifluoromethyl-2H-1-benzopyran-3-carboxylate (Example 10, step 2) (6.21 g, 22.83 mmol) was added. After stirring at −15 ° C. for 1 hour, the solution was allowed to warm to room temperature and stirred for 16 hours. The solution was added dropwise into ice (500 mL) with thorough stirring and extracted with diethyl ether (2 x 250 mL). The ether phases were combined and washed with water (2 x 250 mL), saturated sodium bicarbonate (2 x 250 mL), and brine (2 x 250 mL). Hexane (50 mL) was added and the solution was dried over sodium sulfate. The solvent was removed in vacuo to yield an ester as a yellow solid (7.41 g, 87%): mp 97.2-98.4 ° C. 1 H NMR (CDCl 3, 300 MHz) 7.97 (dd, 1H, J = 8.6, 2.2.Hz), 7.92 (d, 1H, J = 2.2 Hz), 7.73 (s, 1H) 7.17 (d, 1H, J = 2.2 Hz) 5.82 (q HF, 1H, J = 7.2 Hz). 4.28-4.39 (m, 2 H). 1.35 (t, 3H, J = 7.0 Hz). FABLRMS m / z 376 (M + Li +, ). Step 2. Preparation of ethyl 6-[[(phenylmethyl) aminosulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylate Sulfonyl chloride (451.0 mg, 1.22 mmol) and benzylamine (600 mg, 5.62 mmol) from step 1 were mixed in diethyl ether (25 mL) for 1 hour at room temperature. The solution was washed with 1N HCl (2 × 25 mL), saturated sodium bicarbonate (2 × 25 mL), and brine (2 × 25 mL). This solution was dried over sodium sulfate and dried in vacuo. Amino sulfonyl was obtained by recrystallization from hexane (431 mg, 84%): mp 128.2-131.9 ° C. 1 H NMR (CDCl 3 , 300 MHz) 7.76 (dd, 1H, J = 8.4, 2.2.Hz), 7.70 (d, 1H, J = 2.2 Hz), 7.67 (s, 1H), 7.12-7.30 (m, 5H) , 7.05 (d, 1H, J = 8.4 Hz), 5.78 (q HF, 1H, J = 7.2 Hz). 4.68 (m, 2 H). 4.19-4.32 (m, 2 H), 1.37 (t, 3 H, J = 7.0 Hz). FABLRMS m / z 442 (M + H < + >,). FABLRMS m / z 442.0936 (M + H < + >, C 20 H 19 F 3 NO 5 S calcd 442.0916). Step 3. Preparation of 6-[[(phenylmethyl) amino] sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid The acid was converted from the ester (step 2) according to a similar method as described in Example 1, step 2: mp 223.3-224.4 ° C. 1 H NMR (CD 3 OD, 300 MHz) 7.31-7.80 (m, 3H), 7.15-7.25 (m, 5H), 7.06 (d, 1H, J = 8.3 Hz), 5.87 (q HF , 1H, J = 7.2 Hz ), 4.11 (s, 2 H). FABLRMS m / z 420 (M + Li + ). FABHRMS m / z 414.0589 (M + H + calculated 414.0623). Analytical Calcd for C 18 H 14 F 3 NO 5 S: C, 52.30; H, 3.41; N, 3.39. Found: C, 52.16; H, 3.44. N, 3.32. Example 50 6-[(dimethylamino) sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid The title compound was prepared by a method similar to that described in Example 49: mp 201.2-202.5 ° C. 1 H NMR (CD 3 OD / 300MHz) 7.90 (s, 1H), 7.82 (d, 1H, J = 2.2Hz), 7.76 (dd, 1H, J = 8.6, 2.2Hz), 7.19 (d, 1H, J = 8.6 Hz), 5.91 (q HF , 1H, J = 7.2 Hz). 2.70 (s, 6 H). FABLRMS m / z 352 (M + H + ). FABLRMS m / z 352.0466 (M + H + calc. 352.0467). Analytical Calcd for C 13 H 12 F 3 NO 5 S: C, 44.45; H, 3. 44; N, 3.99. Found: C, 44.42; H, 3.45. N, 3.96. Example 51 6-aminosulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid The title compound was prepared by a method similar to that described in Example 49: mp 187.9-189.8 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.58-7.88 (m, 3H), 7.12 (d, J = 8.3 Hz), 5.87 (q HF , 1H, J = 7.2 Hz). FABLRMS m / z 324 (M + H + ). FABHRMS m / z 324.0156 (M + H + calculated 324.0154). Analytical calcd. For C 11 H 8 F 3 NO 5 S * 0.74 H 2 O: C, 39.26; H, 2. 84; N, 4.16. Found: C, 39.33; H, 2.82. N, 4.11. Example 52 6- (methylamino) sulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid The title compound was prepared by a method similar to that described in Example 49: mp 207.6-208.6 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.83-7.97 (m, 3H), 7.19 (d, 1H, J = 8.5 Hz), 5.91 (q HF , 1H, J = 7.2 Hz). FABLRMS m / z 338 (M + H + ). FABHRMS m / z 338.0331 (M + H + calculated 338.0310). Analytical Calcd for C 12 H 11 F 3 NO 5 S: C, 42.73; H, 2.99; N, 4.15. Found: C, 42.91; H, 3.06; N, 4.04. Example 53 6-[(4-morpholino) sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid The title compound was prepared by a method similar to that described in Example 49: mp 215.2-219.3 ° C. 1 H NMR (CD 3 OD / 300MHz) 7.88 (s, 1H), 7.81 (d, 1H, J = 2.2Hz), 7.74 (dd, 1H, J = 8.6, 2.2Hz), 5.90 (q HF , 1H, J = 7.2 Hz). 3.54-3.70 (m, 4H), 2.94-2.97 (m, 4H). FABLRMS m / z 394 (M + H + ). FABHRMS 394.0567 (M + H + , C 15 H 15 F 3 NO 6 S calcd 394.0572). Example 54 6-[(1,1-dimethylethyl) aminosulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid The title compound was prepared by a method similar to that described in Example 49: mp 229.3-233.5 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.82-7.87 (m, 3H), 7.12 (d, 1H, J = 8.6 Hz), 5.87 (q HF , 1H, J = 7.2 Hz). 1.18 (s, 9 H). FABLRMS m / z 380 (M + H + ). Analytical Calcd for C 15 H 16 F 3 NO 5 S: C, 47.49; H, 4. 25; N, 3.69. Found: C, 47.95; H, 4. 48; N, 3.55. Example 55 6-[(2-methylpropyl) aminosulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid The title compound was prepared by a method similar to that described in Example 49: mp 190.6-192.4 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.77-7.84 (m, 3H), 7.13 (d, 1H, J = 8.4 Hz), 5.86 (q HF , 1H, J = 7.2 Hz). 2.64 (d, 2H, J = 6.8 Hz), 1.66 (sept, 1H, J = 6.6 Hz), 0.84 (d, 6H, J = 6.6 Hz). FABLRMS m / z 380 (M + H + ). Analytical Calcd for C 15 H 16 F 3 NO 5 S: C, 47.49; H, 4. 25; N, 3.69. Found: C, 47.61; H, 3. 34; N, 3.55. Example 56 6-methylsulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of 6-chlorosulfonyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid To chlorosulfonic acid (50.0 mL) cooled to -15 ° C, 2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid (Example 10) (4.0 g, 16.7 mmol) was added. After stirring at −15 ° C. for 1 hour, the solution was allowed to warm to room temperature and stirred for 16 hours. The resulting solution was added dropwise on ice (100 mL) with two diethyl ether (2 × 75 mL) extracts. The diethyl ether phases were combined, washed with water (2 x 75 mL) and brine (2 x 75 mL), dried over sodium sulfate and concentrated in vacuo. The resulting solid was triturated with hexane-ethyl acetate (9: 1, 100 mL). 6-chlorosulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid was isolated as a white solid: mp 169-174 ° C. 1 H NMR (CD 3 OD / 300 MHz) 8.18 (d, 1H, J = 8.7 Hz), 6.00 (q, 1H, J = 6.6 Hz). EIHRMS m / z 324.9977 (M + , calculated 324.9994). Step 2. Preparation of 6-methylsulfonyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid A slurry of chlorosulfonyl intermediate (Example 49, step 1) (493 mg, 1.44 mmol), sodium bicarbonate (362 mg, 4.32 mmol) and sodium bisulfite (181 mg, 1.44 mmol) in water (1.5 mL) was added for 1.5 hours. Heat to 60 ° C. and then bromo acetic acid (212 mg, 1.55 mmol) was added. The resulting suspension was heated to reflux, followed by addition of sodium hydroxide solution (50% NaOH solution, 0.10 mL) and water (3.0 mL). The solution was refluxed for 8 hours, cooled to room temperature and acidified to pH 1 with 1N aqueous hydrochloric acid solution. This solution was extracted with ethyl acetate (2 × 25 mL). The combined ethyl acetate phases were washed with 1N aqueous hydrochloric acid solution (2 × 25 mL), water (2 × 25 mL) and brine (2 × 25 mL), dried over sodium sulfate, filtered and concentrated in vacuo to give the title compound as a gray solid. Obtained (231 mg, yield 50%): mp 208.3-212.4 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.97 (d, 1H, J = 2.2 Hz), 7.91 (1H, dd, J = 8.7, 2.2 Hz), 7.19 (d, 1H, J = 8.7 Hz), 5.91 ( q HF , 1H, J = 7.2 Hz. 3.11 (s, 1 H). HRLRMS m / z 321 (M−H). Analytical Calcd for C 12 H 9 F 3 O 5 S * 0.61H 2 O: C, 43.26; H, 3.09; N. Found: C, 43.24; H, 3.09. Example 57 8-chloro-6-[[(phenylmethyl) amino] sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid The title compound was prepared by a method similar to that described in Example 49: mp 167.0-173.8 ° C. 1 H NMR (CD 3 OD / 300MHz) 7.78 (s, 1H), 7.72 (d, 1H, J = 2,0Hz), 7.44 (s, 1H), 7.15-7.23 (m, 5H), 6.01 (q HF , 1H, J = 7.2 Hz), 4.08-4.15 (m, 2H). FABLRMS m / z 454 (M + Li + ). Analytical Calcd for C 16 H 13 ClF 3 NO 5 S: C, 48.28; H, 2.93; N, 3.13. Found: C, xx; H, xx; N, xx. Example 58 6-N, N-diethylaminosulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid The title compound was prepared by a method similar to that described in Example 49: mp 238-240 ° C. 1 H NMR (CD 3 OD / 300MHz) 7.88 (s, 1H), 7.85 (d, 1H, J = 2.2Hz), 7.79 (dd, 1H, J = 8.5, 2.2Hz), 7.14 (d, 1H.J = 7.3 Hz), 1.11 (t, 3H, J = 7.3 Hz). FABHRMS m / z 380.0763 (M + H + , calculated 380.0780). Analytical Calcd for C 15 H 16 F 3 NO 4 S: C, 47.49; H, 4. 25; N, 3.69. Found: C, 47.62; H, 4. 30; N, 3.72. Example 59 6-phenylacetyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl 6-phenylacetyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylate 2-Trifluoromethyl-2H-1-benzopyran-3-carboxylic acid (Example 10) (1.32 g, 4.85 mmol) was cooled to 0 ° C. in dichloromethane (50 mL). Aluminum chloride (2.58 g, 19.5 mmol) was added to give a dark red solution as a result. A solution of phenylacetyl chloride (1.8 g, 12.1 mmol) in dichloromethane (10.0 mL) was added dropwise over 40 minutes. This solution was allowed to warm to rt and stirred for 16 h. This solution was poured into ice (200 mL) and extracted with diethyl ether (2 × 100 mL). This diethyl ether phase was combined and extracted with water (1 × 100 mL), 1N HCl (2 × 100 mL), and saturated sodium bicarbonate (1 × 100 mL). Hexane (20 mL) was added and the solution was extracted with brine (1 x 100 mL). This solution was dried over sodium sulfate and the solvent was removed in vacuo. The crude ester was purified by flash chromatography on silica gel (using ethyl acetate as eluent) to yield the above ester, recrystallized from diethyl ether / hexane (830 mg, 44%): mp 136.2-138.0 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.98 (dd, 2H, J = 8.4, 2.0Hz), 7.90 (d, 1H, J = 2.0Hz), 7.29 (s, 1H), 7.22-7.38 (m, 5H) , 7.02 (d, 1H, J = 8.4 Hz), 5.75 (q HF , 1H, J = 7.2 Hz), 4.25-4.40 (m, 2H), 4.21 (s, 2H), 1.34 (t, 3H, J = 7.0 Hz). FABLRMS m / z 391 (M + H + ). Step 2. Preparation of 6-phenylacetyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid The acid was converted from the ester (step 1) according to a similar method as described in Example 1, step 2: mp 159.0-164.0 ° C. 1 H NMR (CD 3 OD / 300MHz) 8.04-8.16 (m, 3H), 7.87 (s, 1H), 7.05-7.30 (m, 5H), 5.86 (q HF , 1H, J = 7.2 Hz), 4.31 ( s, 2H). FABLRMS m / z 363 (M + H + ). Analytical calcd. For C 19 H 13 F 3 O 4 * 0.29H 2 O: C, 62.08; H, 3.73. Found: C, 62.04; H, 4.03. Example 60 6- (2,2-dimethylpropylcarbonyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid The title compound was prepared by a method similar to that described in Example 59: mp 198-200 ° C. 1 H NMR (CD 3 OD / 300MHz) 7.98-8.06 (m, 2H), 7.88 (s, 1H), 7.07 (d, 1H, J = 8.9 Hz), 5.86 (q HF , 1H, J = 7.2 Hz) , 2.88 (s, 2 H), 1.05 (s, 9 H). FABHRMS m / z 343.1175 (M + H + , requires C 17 H 18 F 3 O 4 343.1157). Analytical Calcd for C 17 H 17 F 3 O 4 : C, 59.65; H, 5.01. Found: C, 59.70; H, 4.97. Example 61 6,8-dichloro-7-methoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl 7-methoxy-2-trifluoromethyl-benzopyran-2H-3-carboxylate 4-methoxysalicylaldehyde (2.38 g, 15.64 mmol), K 2 CO 3 (2.16 g, 15.64 mmol) and ethyl 4,4,4-trifluorocrotonate (2.8 mL, 3.16 g, 18.77 mmol) It was dissolved in DMF (10 mL). The reaction was stirred at rt for 24 h, diluted with water and extracted with Et 2 O. The combined Et 2 O phases were washed with water, dried over MgSO 4 and concentrated in vacuo to afford an oil. Grinding with hexanes led to crystallization. Vacuum filtration gave the solid to give an ester as a pale brown crystalline solid (1.80 g, 38%): mp 78-80 ° C. 1 H NMR (CDCl 3 / 300MHz ) δ7.69 (s, 1H), 7.14 (d, 1H, J = 8.1Hz), 6.59-6.50 (m, 2H), 5.68 (q, 1H, J = 7.1Hz) , 4.39-4.24 (m, 2H), 3.82 (s, 3H), 1.34 (t, 3H, J = 7.3 Hz). FABLRMS m / z 303 (M + H). FABHRMS m / z 303.0849 (M + H calculated 303.0844). Analytical Calcd for C 14 H 13 F 3 O 4 : C, 55.63; H, 4.34. Found: C, 55.47; H, 4.31. Step 2. Preparation of ethyl 6,8-dichloro-7-methoxy-2-trifluoromethyl-benzopyran--2H-3-carboxylate Chlorine gas (excess) was added to a stirred solution of HOAc (30 mL) of ester (step 1) (1.35 g, 4.47 mmol) until yellow remained. After 20 minutes, the reaction was blown with nitrogen to make the reaction straw. Zinc (0.86 g, 13.40 mmol) was added to this solution with vigorous stirring. After 45 minutes additional zinc (0.86 g, 13.40 mmol) was added and the reaction stirred overnight. This crude mixture was diluted with EtOH and filtered through diatomaceous earth. The filtrate was concentrated in vacuo to afford crystalline material. This solid was dissolved in EtOAc, washed with 2N HCl, brine, dried over MgSO 4, filtered and concentrated in vacuo to afford an oil. This oil was dissolved in a minimum amount of isooctane to induce crystallization. The suspension was vacuum filtered to give a tan needle (1.078 g) that was recrystallized from isooctane, which gave a dichloro ester as a tan crystal (0.71 g, 43%) of purity suitable for use in the next step: mp 113.3-115.1 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.88 (s , 1H), 7.63 (s, 1H), 6.02 (q, 1H, J = 6.8Hz), 4.38-4.22 (m, 2H), 3.93 (s, 3H), 1.31 (t, 3H, J = 7.1 Hz). 19 F NMR (acetone -d 6/282 MHz) -80.00 ( d, J = 7.2Hz). Step 3. Preparation of 6,8-dichloro-7-methoxy-2-trifluoromethyl-benzopyran-2H-3-carboxylic acid To a stirred solution of the dichloro ester (0.686 g, 1.848 mmol) from step 2 in THF (10 mL) and EtOH (3 mL) was added NaOH (0.81 mL, 2.03 mmol) in 2.5M aqueous solution. After stirring overnight, the reaction was partially condensed, diluted with water and washed with diethyl ether. Nitrogen was blown into the resulting aqueous phase and acidified with 2N HCl solution to make the solution cloudy. This suspension was filtered to give the title compound as a white powder (0.599 g, 88%): mp 195.6-199.1 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.90 (s, 1H), 7.64 (s, 1H), 6.01 (q, 1H, J = 6.8Hz), 3.94 (s, 3H), 19 F NMR (CDCL 3/282 MHz) -79.63 (d, J = 7.1 Hz). FABLRMS m / z 349 (M + Li). EIHRMS m / z 341.9681 (M < + >, calculated 341.9673). Analytical Calcd for C 12 H 7 Cl 2 F 3 O 4 : C, 42.01; H, 2.06. Found: C, 41.76; H, 2.14. Example 62 2-Trifluoromethyl-2H-naphtho [1,2-b] pyran-3-carboxylic acid Step 1. Preparation of ethyl 2-trifluoromethyl-3H-naphthopyran-carboxylate A mixture of 2-hydroxy-1-naphthaldehyde (8.6 g, 0.050 mmol) and ethyl 4,4,4-trifluorocrotonate (9.2 g, 0.055 mole) was dissolved in anhydrous DMF (10 mL) and dried over anhydrous K. Treated with 2 CO 3 (13.8 g, 0.100 mole). This solution was kept at room temperature for 50 hours and diluted with water. The solution was extracted with ethyl acetate and the combined extracts were washed with brine, dried over anhydrous MgSO 4 and concentrated in vacuo to yield 4.8 g of oil. This oil was purified by HPLC eluting with hexanes: ethyl acetate (30: 1). The appropriate aliquot was concentrated to yield 1.6 g (10%) of naphthopyran ester as a yellow solid. Step 2. Preparation of 2-trifluoromethyl-3H-naphthopyran-carboxylate The solution of ester (0.8 g, 2.5 mmol) from step 1 was dissolved in 40 mL of ethanol and 10 mL of tetrahydrofuran, treated with sodium hydroxide (2.5N, 10 mL, 25 mmol) and stirred at room temperature for 16 hours. The reaction mixture was acidified with 1.0N HCl, and then the solid formed was separated by filtration. This solid was washed with 20 mL of water to yield 0.7 g (95%) of the title compound as a yellow solid: mp 245.9-248.6 ° C. 1 H NMR (acetone -d 6 / 300MHz) 8.57 (s , 1H), 8.28 (d, 1H, J = 8.7Hz), 8.03 (d, 1H, J = 9.0Hz), 7.93 (d, 1H, J = 8.7), 7.67 (m, 1 H), 7.50 (m, 1 H), 7.28 (d, 1 H, J = 7.2 Hz). FABHRMS m / z 295.0561 (M + H + , calculated 295.0582). Analytical calcd. For C 15 H 9 O 3 F 3 + 3.31% H 2 O: C, 59.21; H, 3.35. Found: C, 59.17; H, 3.07. Example 63 2-Trifluoromethyl-3H-naphtho [2,1-b] pyran-3-carboxylic acid 2-hydroxy-naphth-1-aldehyde was converted to the title compound by a method similar to that described in Example 1: mp 244.7-249.8 ° C. 1 H NMR (CDCl 3 / 300MHz) 8.61 (s, 1H), 8.09 (d, 1H, J = 8.3Hz), 7.90 (d, 1H, J = 8.9Hz), 7.82 (d, 1H, J = 8.3Hz ), 7.63 (t, 1H, J = 8, 1 Hz), 7.47 (t, 1H, J = 8.1 Hz), 7.23 (d, 1H, J = 9.1 Hz), 5.84 (q, 1H, J = 6.8 Hz) . 19 F NMR (CDCl 3/282 MHz) -79.56 (d, J = 7.3Hz). FABLRMS m / z 295 (M + H). FABHRMS m / z 295.0560 (M + H, calculated 295.0582). Analytical Calcd for C 15 H 9 F 3 O 3 : C, 61.23; H, 3.08. Found: C, 60.85; H, 3.12. Example 64 2-trifluoromethyl-2H-naphtho [2,3-b] pyran-3-carboxylic acid 3-hydroxynaphthalene-2-carboxylic acid was converted to 3-hydroxynaphthalene-2-carboxaldehyde by a method similar to that described in Example 24, steps 1 and 2. 3-hydroxynaphthalene-2-carboxaldehyde was converted to the title compound by a method similar to that described in Example 1: mp decomposition> 300 ° C. 1 H NMR (CD 3 OD / 300MHz) 7.99 (s, 1H), 7.90 (s, 1H), 7.84 (d, 1H, J = 8.2Hz), 7.74 (d, 1H, J = 8.2Hz), 7.50 ( t, 1H, J = 8.2 Hz, 7.39 (t, 1H, J = 8.2 Hz), 7.34 (s, 1H), 5.77 (q, 1H, J = 6.6 Hz). EIHRMS m / z 294.0474 (M < + >, calculated 294.0504). Example 65 6-chloro-2-trifluoromethyl-2H-1-benzothiopyran-3-carboxylic acid Step 1. Synthesis of 5-chloro-thiosalicylaldehyde Tetramethylethylenediamine (TMEDA) (10.44 mL, 8.035 g, 69.15 mmol) was added to n-BuLi (43.22 mL, 69.15 mmol) with an injector and the solution was cooled to 0 ° C. A solution of 4-chlorothiophenol (5.00 g, 34.57 mmol) in cyclohexane (25 mL) was added with stirring for 1 hour. The resulting tan slurry was stirred at rt overnight, cooled to 0 ° C., and DMF (2.94 mL, 2.78 g, 38.03 mmol) was added via injector over 2 minutes. The resulting gummy slurry was stirred for 30 hours at room temperature to give a powdery suspension. 2N HCl and ice mixture were added to this mixture until the pH was acidic (pH = 1). During the addition, the mixture was warmed until it first became red and then light yellow. This mixture was extracted with ethyl acetate. The combined organic phases were washed with brine, dried over MgSO 4 , filtered and concentrated in vacuo to give a bright reddish brown oil. This oil was triturated with hexanes to give a reddish brown semisolid. This semisolid is purified by plug flash chromatography eluting with 1: 1 hexanes: dichloromethane on silica gel to give 5-chloro-thiosalicylaldehyde (0.858 g, 14%) as a dark yellow solid suitable for use without further purification. Was calculated. Step 2. Preparation of ethyl 6-chloro-2-trifluoromethyl-benzo-1-thiopyran-2-H-3-carboxylate 5-Chloro-thiosalicylaldehyde (step 1) (0.84 g, 4.86 mmol) was added to DMF (3 mL) and 4,4,4-trifluorocrotonate (1.10 mL, 1.22 g). While stirring, K 2 CO 3 (0.67 g, 4.86 mmol) was added to bring the reaction to a deep red color. After stirring at room temperature overnight, the reaction was diluted with diethyl ether and washed with water, saturated NaHCO 3 solution, aqueous KHSO 4 solution (0.25M), brine, dried over MgSO 4 , filtered and concentrated in vacuo to give an oil. Obtained. The oil was purified by flash chromatography (5: 1; hexanes: ethyl acetate) and concentrated to ethyl 6-chloro-2-trifluoromethyl-benzo-1-thiopyran-2-H-3-car as a light orange solid. Cyclate was obtained (0.492 g, 31%): mp 94.6-97.4 ° C. 1 H NMR (acetone -d 6 / 300MHz) δ 8.01 ( s, 1H), 7.71 (d, 1H, J = 2.2 Hz), 7.50 (d, 1H, J = 8.5Hz), 7.44 (d of d, 1H , J = 2.3, 8.3 Hz), 5.07 (q, 1H, J = 8.5 Hz), 4.42-4.23 (m, 2H), 1.35 (t, 3H, J = 7.1 Hz). FABLRMS m / z 329 (M + Li). Step 3. Preparation of 6-Chloro-2-trifluoromethyl-benzo-1-thiopyran-2-H-3-carboxylic acid To a stirred solution of the ester (0.413 g, 1.280 mmol) from step 2 in THF: EtOH: H 2 O (7: 2: 1, 10 mL) was added with stirring NaOH solution (0.56 mL, 1.408 mmol) of 2.5N solution. It was. After stirring overnight, the reaction was partially concentrated in vacuo to remove the organic solvent, diluted with water and washed with several portions of diethyl ether. The stirred aqueous phase with concentrated hydrochloric acid was acidified to precipitate a downy yellow precipitate. Vacuum filtration of the suspension gave 6-chloro-2-trifluoromethyl-benzo-1-thiopyran-2H-3-carboxylic acid as a yellow powder: mp 188.8-198.7 ° C. 1 H NMR (acetone -d 6 / 300MHz) δ 8.02 ( s, 1H), 7.71 (d, 1H, J = 2.22Hz), 7.50 (d, 1H, J = 8.5Hz), 7.44 (d of d, 1H , J = 2.22, 8.5Hz), 5.05 (q, 1H, J = 8.6Hz), 19 F NMR ( acetone -d 6 / 282MHz) d -75.22 ( d, J = 8.7Hz). FABLRMS m / z 301 (M + Li); ESLRMS (neg. Ion) m / z 293 (MH). Example 66 (S) -6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 6-chloro-2-trifluoromethyl-2H-1 -benzopyran-3-carboxylic acid (Example 1, Step 2) (12.00 g, 43.07 mmol) in methyl-tert-butyl ether (30 mL) and (S ) n-heptane (200 mL) was added slowly to a solution of (-)-α-methylbenzylamine (2.61 g, 21.54 mmol) until the mixture became cloudy. The mixture was heated to boiling (steam electrolyzer) and left for 24 hours to allow crystals to form. The suspension was filtered to give crystalline product (5.5 g), which was recrystallized from methyl-tert-butyl ether (30 mL) and n-heptane (200 mL) to give a white solid (3.1 g) by filtration. . This solid was dissolved in EtOAc (100 mL) and washed with 1N hydrochloric acid (50 mL) and brine (2 × 50 mL), dried over MgSO 4 and concentrated in vacuo to give a white solid. This solid was recrystallized from methyl-tert-butyl ether / n-heptane to yield the title compound as a highly abundant isomer of a white solid (2.7 g, 45%): mp 126.7-128.9 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.78 (s, 1H), 7.3-7.1 (m, 3H), 6.94 (d, 1H, J = 8.7Hz), 5.56 (q, 1H, J = 6.9Hz). Analytical Calcd for C 11 H 6 O 3 F 3 Cl: C, 47.42; H, 2. 17; N, 0.0. Found: C, 47.53; H, 2.14; N, 0.0. This compound was quantified to have an optical purity of 90% or more. Optical purity quantification method To a solution of free acid (title compound) (0.005 g, 0.017 mmol) in ethyl acetate (1.5 mL) in vitro was added (trimethylsilyl) diazomethane (30 μl of 2.0 N in hexane, 60 mmol). The resulting yellow solution was warmed until it started to boil gently and then left to stand for 0.8 hours to cool to room temperature. While vigorously mixing, the solution was immersed in 1N aqueous HCl (1.5 mL) and cooled. The phases were separated and the ether ether acetate fraction (0.3 mL) was transferred to a vial, concentrated under nitrogen stream, diluted with hexane (1 mL total) and the sample (10 μl) analyzed by chiral chromatography. HPLC used a Daicel Chiralpak AD column eluting at a flow rate of 0.5 mL / min with 10% isopropanol-hexane using a UV detector set at 254 nm. Example 67 (S) -6-trifluoromethoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 6-trifluoromethoxy-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid (Example 16) in methyl-tert-butyl ether (100 mL) heated with a steam electrolyzer (17.72 g) , 54.00 mmol) and (-)-cinconidine (7.95 g, 27.04 mmol) were added n-heptane (200 mL). The mixture was heated to boiling (steam electrolyzer) and left for 4 hours to allow crystals to form. The suspension was filtered to give crystalline solid (18.7 g). This solid was dissolved in 2-butane (30 mL) and then added to n-heptane (500 mL). After standing for 16 hours, the resulting suspension was filtered to give a white solid (10.3 g). This solid was dissolved in EtOAc (150 mL) and washed with 1N hydrochloric acid (100 mL) and brine (2 x 50 mL), dried over MgSO 4 , filtered and concentrated in vacuo to give a viscous yellow oil (5.2 g, 59%). ): 1 H NMR (acetone -d 6 / 300MHz) 7.16 (s , 1H), 6.77 (d, 1H, J = 2.7Hz), 6.94 (d, 1H, J = 8.7Hz), 6.64 (m, 1H) , 6.39 (d, 1H, J = 8.7 Hz), 5.13 (q, 1H, J = 7.2 Hz). Analytical Calcd for C 12 H 6 O 4 F 6 : C, 43.92; H, 1. 84; N, 0.0. Found: C, 43.79; H, 1.83; N, 0.0. This compound was quantified to have an optical purity of 90% or more. Chiral purity was quantified as described in Example 66. Example 68 (S) -6-chloro-7- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 6-chloro-7- (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid (Example 8) (11.4 g, 34.1 mmol) and (S)- N-heptane (200 mL) was added to a solution of (-)-2-amino-3-phenyl-1-propanol (2.57 g, 17.00 mmol) and the mixture was left for 16 h. The resulting suspension was filtered to give a solid (3.8 g). This solid was recrystallized from 2-butane (20 mL) and n-heptane (200 mL) and filtered to give a white solid (3.0 g). This solid was dissolved in EtOAc (100 mL) and washed with 1N hydrochloric acid (50 mL) and brine (2 × 50 mL), dried over MgSO 4 and concentrated in vacuo to give a white solid. This solid was recrystallized from n-heptane to give the title compound having high optical purity as a crystalline solid (1.7 g, 30%): mp 175.4-176.9 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.86 (s , 1H), 7.52 (s, 1H), 7.12 (s, 1H), 5.83 (q, 1H, J = 7.1Hz), 1.48 (s, 9H) . Analytical Calcd for C 15 H 14 O 3 F 3 Cl: C, 53.83; H, 4. 22; N, 0.0; Cl, 10.59. Found: C, 53.78; H, 4. 20; N, 0.0; Cl, 10.65. This compound was quantified to have an optical purity of 90% or more. Chiral purity was quantified as described in Example 66. Example 69 6-[[(2-furanylmethyl) amino] sulfonyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid The title compound was prepared by a method similar to that described in Example 49: mp 170-173 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.78 (s, 1H), 7.66-7.76 (m, 2H), 7.18-7.22 (m, 1H), 7.00-7.08 (m, 1H), 6.12-6.18 (m, 1H), 6.02-6.06 (m, 1H), 5.85 (q, 1H, J = 7.0 Hz), 4.13 (s, 2H). EIHRMS m / z 403.0332 (M < + >, 403.0337). Example 70 6-[(phenylmethyl) sulfonyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was prepared by the method in the same manner as described in Example 56: mp 172-176 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.73 (s, 1H), 7.43-7.56 (m, 2H), 7.21-7.33 (m, 3H), 7.20-7.21 (m, 3H), 5.88 (q, 1H, J = 7.0 Hz), 4.83 (s, 2 H). EIHRMS m / z 398.0399 (M < + >, 398.0436). Example 71 6-[[(phenylethyl) amino] sulfonyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was prepared by the method in the same manner as described in Example 49: mp 187-190 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.82 (s, 1H), 7.74-7.90 (m, 2H), 7.08-7.29 (m, 6H), 5.89 (q, 1H, J = 6.8), 3.12 (t, 2H, J = 7.3 Hz), 2.72 (t, J = 7.3 Hz). EIHRMS m / z 427.0675 (M < + >, 427.0701). Example 72 7-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 4-chlorosalicylic acid was converted to 3-chlorosalicylaldehyde by zalcha similar to that described in Example 24, steps 1 and 2. 3-chlorosalicylaldehyde was converted to the title compound by a method similar to Example 1: mp 175.2-177.6 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.90 (s , 1H), 7.51 (d, 1H, J = 7.8Hz), 7.12 (m, 2H), 5.86 (q HF, 1H, J = 7.2Hz). FABHRMS m / z 285.0114 (M + Li, calculated 285.0118). Analytical Calcd for C 11 H 6 ClF 3 O 3 : C, 47.72; H, 2. 17; Cl, 12.72. Found: C, 47.54; H, 2. 37; Cl, 12.85. Example 73 6-chloro-8-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of 3-iodo-5-chlorosalicylaldehyde N-iodosuccinimide (144.0 g, 0.641 mmol) was added to a solution of 5-chlorosalicylaldehyde (100 g, 0.638 mole) in dimethylformamide (400 mL). The reaction mixture was stirred for 2 days at room temperature. Additional N-iodosuccinimide (20 g, 0.089 mole) was added and stirring continued for another two days. The reaction mixture was diluted with ethyl acetate (1 liter) and washed with hydrochloric acid (300 mL, 0.1 N), water (300 mL), sodium thiosulfate (300 mL, 5%), and brine (300 mL). It was dried over MgSO 4 and dried to concentrate and yield the required aldehyde as a light yellow solid (162 g, 90%): mp 84.8-86.7 ° C .. 1 H NMR (CDCl 3 / 300MHz ) 11.67 (s, 1H), 9.71 (s, 1H), 7.92 (d, 1H, J = 2.5Hz), 7.54 (d, 1H, J = 2.6Hz). FABLRMS m / z 281.0 (MH), FSHRMS m / z 280.8851 (MH, calculated 280.88630). Step 2. Preparation of ethyl 6-chloro-8-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate 5-chloro-3-iodosalicylaldehyde (20 g, 70.8 mmol), ethyl 4,4,4-trifluorocrotonate (17.85 g, 106 mmol), and triethylamine (14.33 g, 142 mmol) were DMSO (200 mL). )). The reaction mixture was stirred at 90 ° C. for 3 days. The reaction mixture was poured into ethyl acetate (800 mL). This was extracted with 10% HCl (2 × 200 mL), saturated aqueous NaHCO 3 (2 × 200 mL), and water (2 × 200 mL). The ethyl acetate phase was dried over MgSO 4, filtered and evaporated to yield a brown solid. Then run through a silica plug with ethyl acetate-hexane (1:20). The solvent was evaporated to yield a yellow solid which was recrystallized from hexane to give an ester as a white solid (19.61 g, 64%): mp 92.1-93.9 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.71 (d, 1H, J = 2.2Hz), 7.56 (s, 1H), 7.20 (d, 1H, J = 2.2Hz), 5.81 (q, 1H, J = 6.7Hz ), 4.37-4.29 (m, 2H), 1.35 (t, 3H, J = 7.2 Hz). FABLRMS m / z 431.9 (M−H). EIHRMS m / z 431.9269 (M−H, calculated 431.9237). Step 3. Preparation of 6-Chloro-8-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid The acid was prepared by an analogous method as described in Example 1, Step 2, ester (step 2): mp 220-223 ° C. 1 H NMR (CD 3 OD / 300MHz) 7.77 (d, 1H, J = 2.2 Hz), 7.71 (s, 1H), 7.41 (d, 1H, J = 2.2 Hz), 5.87 (q, 1H, J = 7.0 Hz). EIHRMS m / z 403.8893 (MH, calculated 403.8923). Analytical Calcd for C 11 H 5 ClF 3 IO 3 : C, 32.66; H, 1.25. Found: C, 33.13; H, 1.29. Example 74 6-Bromo-6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl 8-bromo-6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylate 3-bromo-5-chlorosalicylaldehyde (1.9 g, 4.2 mmol), potassium carbonate salt (0.58 g, 4.2 mmol), and ethyl 4,4,4-trifluorocrotonate (0.79 g, 4.7 mmol) The mixture of was stirred at 95 ° C. for 18 h in N, N-dimethylformamide (5 mL). The combined organic extracts were dried over MgSO 4 and concentrated, then the mixture was eluted with ethyl acetate-hexane (1: 4) through a pad of silica and filtered. The eluate was concentrated and the light yellow solid was recrystallized from cold hexane (0.43 g, 26%): mp 101.0-102.2 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.90 (s , 1H), 7.65 (d, H, J = 2.4Hz), 7.61 (d, H, J = 2.4Hz), 6.03 (q HF, 1H, J = 6.9 Hz), 4.34 (m, 2H), 1.33 (t, 3H, J = 7.5 Hz). FSHRMS m / z 384.9435 (M−H, calculated 384.9454). Analytical Calcd for C 13 H 9 BrClF 3 O 3 : C, 40.50; H, 2.35. Found: C, 40.61; H, 2.40. Step 2. Preparation of 8-Bromo-6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid Ethyl 8-bromo-6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylate (0.3 g), ethanol (15 mL), tetrahydrofuran (10 mL) and sodium hydroxide solution (10 mL , 2.5N) was stirred at rt for 16 h. Hydrochloric acid (1 N) was added until the mixture appeared acidic on pH paper. Water was added to give a precipitate which was collected by filtration to give the title compound as a white solid (0.2 g, 72%): mp 227.8-228.9 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.90 (s , 1H), 7.65 (dd, 2H, J = 2.4 and J = 28.8Hz), 6.00 (q HF, 1H, J = 7.2Hz). FSBHRMS m / z 356.9134 (M + H, calculated 356.9141). Analytical Calcd for C 11 H 5 BrClF 3 O 3 : C, 39.96; H, 1.41. Found: C, 37.05; H, 1.33. Example 75 6-formyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of 6-formyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid In a 50 mL round bottom flask, 5-formylsalicylaldehyde (3.21 g, 21.39 mmol), ethyl 4,4,4-trifluorocrotonate (3.50 mL, 3.96 g, 23.53 mmol), dimethylformamide (15 mL) and Potassium carbonate (2.95 g, 21.39 mmol) was added thereto and heated to 60 ° C. for 12 hours. Additional ethyl 4,4,4-trifluorocrotonate (3.50 mL, 3.96 g, 23.53 mmol) was added and the reaction heated at 75 ° C. for 16 h. After cooling to room temperature, the reaction was partitioned between H 2 O and diethyl ether. The organic phase was washed with NaHCO 3 solution, KHSO 4 solution (0.25M), brine and treated with decolorized carbon (heated mildly). The resulting black suspension was dried over MgSO 4, vacuum filtered through diatomaceous earth and concentrated in vacuo to yield an orange crystalline material. This material was recrystallized from hot hexane to give the above ester (1.51 g, 24%) as orange crystals: mp 84.3-86.2 ° C. 1 H NMR (acetone -d 6 / 300MHz) 9.96 (s , 1H), 8.06 (d, 1H, J = 2Hz), 8.02 (s, 1H), 7.99 (dd, 1H, J = 8.5 and 2.0Hz), 7.24 (d, 1H, J = 8.5 Hz), 5.99 (q, 1H, J = 7.1 Hz), 4.43-4.25 (m, 2H), 1.34 (t, 3H, J = 7.3 Hz). FABLRMS m / z 301 (M + H). EIHRMS m / z 300.0605 (M < + >, 300.0609). Analytical Calcd for C 14 H 11 F 3 O 4 : C, 56.01; H, 3.69. Found: C, 56.11; H, 3.73. Step 2. Preparation of 6-formyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Ester (step 1) was converted to the acid in a similar manner as described in Example 1, step 2: mp 211.3-215.7 ° C. 1 H NMR (acetone-d 6 / 300MHz) 9.97 (s, 1H), 8.07 (d, 1H, J = 2.0Hz), 8.03 (s, 1H), 8.00 (dd, 1H, J = 8.3, 2.0Hz) . FABLRMS m / z 273 (M + H). EIHRMS m / z 272.0266 (M < + >, calculated 272.0296). Analytical Calcd for C 12 H 7 F 3 O 4 : C, 52.95; H, 2.59. Found: C, 52.62; H, 2. 58. Example 76 6-chloro-8-formyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of 4-chloro-2,6-bis (hydroxymethyl) phenol Potassium hydroxide (84.82 g, 1.30 mole) was dissolved in H 2 O (200 mL) in a 2-liter three-necked flask equipped with a Dermocouple, a mechanical stirrer and a stopper. While stirring, 4-chlorophenol (128.56g, 1.0mole) was added cooling (ice electrolyzer), and temperature was raised to 26 degreeC. Formalin (230 mL of 37% aqueous solution, 2.83 mole) was added dropwise keeping the temperature below 25 ° C. The reaction was warmed to 35 ° C. for 48 hours. Aqueous acetic acid (1.40 mole, 80.0 mL, 84.1 g) in 800 mL H 2 O was added to this solution to make the solution cloudy. The suspension was vacuum filtered to give a tan solid. This solid was stirred with acetone (100 mL) and insoluble solids were collected by vacuum filtration. This solution was diluted with hexane to yield several crops of the diol as fine tan needles: mp 160.6-163.3 ° C. 1 H NMR (acetone -d 6 / 300MHz) 6.69 (s , 2H), 4.48 (s, 4H), 7.88 (d, 1H, J = 6.9Hz), 7.75 (d, 1H, J = 2.6Hz). 6.08 (q, 1H, J = 6.9 Hz). FSLRMS m / z 206 (M + NH 4 + ). ESHRMS m / z 187.0131 (M−H, calculated 187.0162). Step 2. Preparation of 5-chloro-3-formyl-salicyaldehyde Manganese dioxide (139 g, 1.60 mole) was added to a stirred suspension of diol (step 1) in chloroform (1.5 L) in a 2 liter round bottom flask and the resulting suspension was heated to gentle reflux for 10 hours. The reaction was allowed to cool to room temperature, filtered through diatomaceous earth, concentrated in vacuo, pre-adsorbed on silica gel and purified by flash chromatography (hexane / ethyl acetate) to give mustard powdery dialdehyde (22.42 g, 67%). Was: mp 120.7-122.8 ° C. This solid was of a suitable purity for use in the next step without further purification. Step 3. Preparation of ethyl 6-chloro-8-formyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate Dialdehyde (step 2) (1.13 g, 6.14 mmol), dimethyl sulfoxide (6 mL), ethyl 4,4,4-trifluorocrotonate (1.37 mL, 1.55 g, 9.21 mmol) in a round bottom flask equipped with a condenser And a stirred solution of triethylamine (1.71 mL, 1.24 g, 12.28 mmol) was heated to 80 ° C. for 8 hours. After cooling to rt, the reaction was diluted with diethyl ether (100 mL) and the resulting mixture was washed with aqueous sodium bicarbonate solution (3 × 75 mL), 1N HCl solution (3 × 70 mL), and brine (1 × 75 mL) and washed with MgSO Dry over 4, filter and concentrate in vacuo to give a tan powder. This powder was dissolved in hot hexane-ethyl acetate and filtered to remove insoluble matter. After cooling the filtrate, the required ester as tan crystals was obtained by vacuum filtration followed by recrystallization (0.726 g, 35%): mp 118.1-119.7 ° C. This material was of a suitable purity for use without further purification. Step 4. Preparation of 6-Chloro-8-formyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Aqueous NaOH solution (0.41 mL, 1.02 mmol) was added to a stirred solution of the above ester (step 3) (0.284 g, 0.849 mmol) in THF: EtOH: H 2 O (7: 2: 1, 5 mL). After stirring for 40 hours, the reaction was partially concentrated in vacuo to remove organic solvents, diluted with water, washed with diethyl ether, blown with nitrogen to remove traces of diethyl ether, and acidified with concentrated HCl. The suspension was calculated. The suspension was vacuum filtered to afford the title compound as a light yellow powder (0.160 g, 23%). mp 243.3-252.4 ° C. 1 H NMR (acetone -d 6 / 300MHz) 10.39 (s , 1H), 7.98 (s, 1H), 7.88 (d, 1H, J = 2.6Hz), 7.75 (d, 1H, J = 2.6Hz), 6.08 (q, 1H, J = 6.9 Hz). FABLRMS m / z 307 (M + H). ESHRMS m / z 304.9839 (M−H, calculated 304.9828). Analytical Calcd for C 12 H 6 ClF 3 O 4 : C, 47.01; H, 1.97. Found: C, 46.64; H, 1.86. Example 77 6-Bromo-7- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 7- (1,1-dimethylethyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid (Example 12) (0.6 g, 2 mmol), chloroform (50 mL), iron filler ( 0.01 g, 0.2 mmol) and bromine (0.48 g, 3.00 mmol) were refluxed and stirred for 16 hours The mixture was left to cool and washed with brine (2 x 50 mL) After drying over MgSO 4 , the mixture was dried filtered, concentrated in vacuo and the residue ether - by re-crystallization with hexane to give the title compound as a white solid (0.5g, 66%) 1 H NMR ( acetone -d 6 / 300MHz) 7.85 (s , 1H), 7.72 (s, 1H), 7.13 (s, 1H), 5.83 (q, 1H, J = 7.2 Hz), 1.5 (s, 9H) Analytical calculation for C 15 H 14 O 3 F 3 Br: C, 47.52; H, 3.72; N, 21.07. Found: C, 47.42; H, 3.68; N, 21.15. Example 78 5,6-dichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 5,6-dichlorosalicylaldehyde was prepared by the method described in US Pat. No. 3,794,734 (1974, Cragoe, EJ; Schultz, EM). This salicylicaldehyde was converted to the title compound by a method similar to that described in Example 1: mp 211.5-213.5 ° C. 1 H NMR (acetone -d 6 / 300MHz) 8.09 (s , 1H), 7.63 (d, 1H, J = 8.9), 7.12 (d, 1H, J = 8.9Hz), 5.94 (q, 1H, J = 7.0 Hz). ESLRMS m / z 311 (MH). EIHRMS m / z 311.9583 (M < + >, 311.9568). Analytical Calcd for C 11 H 5 Cl 2 F 3 O 3 : C, 42.20; H, 1.61. Found: C, 42.33; H, 1.67. Example 79 6-cyano-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl 6-[(hydroxyimino) methyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate In a 50 mL round bottom flask, hydroxylamine HCl (0.255 g, 3.67 mmol), ethyl 6-formyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 75, step 1) (1.00 g, 3.34 mmol), sodium acetate (0.301 g, 3.67 mole), ethanol (10 mL), and water (2 mL) were added thereto. The reaction was stirred at rt for 18 h and then diluted with water and diethyl ether. The phases were separated and the organic phase was washed with water, brine, dried over MgSO 4 , filtered and concentrated in vacuo to give an orange semicrystalline material. This solid was recrystallized from hot ethyl acetate and isooctane to give the oxime (0.578 g, 55%): mp 113.0-116.2 ° C. 1 H NMR (acetone -d 6 / 300MHz) 10.46 (s , ca.1 exch.), 8.11 (s, 2H), 7.92 (s, 1H), 7.72 (d, 1H, J = 2Hz), 7.68 (dd , 1H, J = 8.5, 2.0 Hz), 7.07 (d, 1H, J = 8.5 Hz), 5.89 (q, 1H, J = 7.1 Hz), 4.43-4.22 (m, 2H), 1.34 (9t, 3H, J = 7.3 Hz). FABLRMS m / z 316 (M + H). EIHRMS m / z 315.0719 (M < + >, 315.0733). Analytical Calcd for C 14 H 12 N 1 F 3 O 4 : C, 53.34; H, 3. 84; N, 4.44. Found: C, 53.85; H, 3. 90; N, 4.19. Step 2. Preparation of ethyl 6-cyano-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate Trifluoroacetic anhydride (0.130 mL, 0.194 g, 0.924 mmol) and tree in an oxime (step 1) (0.264 g, 0.840 mmol) stirred solution in dioxane (4.5 mL) in a 25 mL pear-shape flask Ethylamine (0.140 mL, 0.102 g, 1.008 mmol) was added. The reaction was stirred at rt for 12 h and then heated at 85 ° C. for 4 h. After cooling to room temperature, aqueous HCl (50 mL, 1N HCl) was added and the resulting mixture was extracted with ethyl acetate. The ethyl acetate phase was washed with cooled aqueous HCl (1N), brine, dried over Na 2 S0 4, filtered and concentrated in vacuo to give a pale yellow oil. This oil was provided again under similar reaction conditions. This light yellow oil was dissolved in dioxane (4.5 mL), followed by addition of trifluoroacetic anhydride (0.130 mL, 0.194 g, 0.924 mmol) and triethylamine (0.140 mL, 0.102 g, 1.008 mmol). The reaction was stirred at rt for 3 h, then triethylamine (0.50 mL, 0.36 g, 3.6 mmol) was added and then heated at 85 ° C. for 3 h. After cooling to room temperature, aqueous HCl (50 mL, 1N HCl) was added and the resulting mixture was extracted with ethyl acetate. The ethyl acetate phase was washed with cooled aqueous HCl (1N), brine, dried over Na 2 S0 4, filtered and concentrated in vacuo to give a pale yellow oil. Recrystallization by addition of hexane followed by vacuum filtration gave the title compound (0.101 g, 40%) as light yellow powder: mp 101.6-106.1 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.97 (d , 1H, J = 2.2Hz), 7.95 (s, 1H), 7.82 (dd, 1H, J = 8.5, 2.0Hz), 7.24 (d, 1H, J = 8.5 Hz), 6.01 (q, 1H, J = 7.1 Hz), 4.38-4.24 (m, 2H), 1.34 (t, 3H, J = 7.3 Hz). FABLRMS m / z 298 (M + H). EIHRMS m / z 297.0575 (M < + >, calculated 297.0613). Step 3. Preparation of 6-cyano-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid To a stirred solution of the ester (step 2) (0.077 g, 0.259 mmol) in THF-EtOH-H 2 O (7: 2: 1, 2 mL) in a 5 mL volume pear-shape flask was added an aqueous NaOH solution (2.5 0.13 mL of N solution) was added in portions. After stirring for 6 hours at room temperature, the solution was partially concentrated in vacuo to remove most of the THF and EtOH. The resulting solution was diluted with water and washed with diethyl ether. Nitrogen was blown into the resultant aqueous phase to remove traces of diethyl ether, and acidified with concentrated HCl to yield a viscous suspension. This suspension was extracted with diethyl ether and the ether was dried over MgSO 4, filtered and concentrated in vacuo to give a pale yellow oil. This oil was recrystallized from methylene chloride-hexane to give the title compound as a tan powder (0.041 g, 59%): mp 185.1-186.1 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.99-7.94 (m , 2H), 7.83 (dd, 1H, J = 8.5, 2.0Hz), 7.25 (d, 1H, J = 8.5Hz), 5.99 (q, 1H, J = 7.0 Hz). FABLRMS m / z 270 (M + H). EIHRMS m / z 269.0316 (M < + >, 269.0300). Example 80 6-hydroxymethyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Cooled of 6-formyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid (Example 75, Step 2) in THF (1 mL) and ethanol (1 mL) in a 10 mL round bottom flask. (Ice electrolyzer) NaBH 4 (0.020 g, 0.528 mmol) was added in two portions to the stirred solution. The reaction was allowed to warm to room temperature and further NaBH 4 (0.050 g, 1.322 mmol) was added. Total reaction time was 3 hours. The reaction was immersed in an aqueous HCl solution (1N solution), cooled and extracted with chloroform. The organic phase was dried over MgSO 4, filtered and concentrated in vacuo to give a foam. This crude product was purified by flash chromatography (silica gel 60, eluent 1: 1, hexane-ethyl acetate (containing 2% acetic acid)). The product collected from chromatography was recrystallized from hexane and ethyl acetate and collected by vacuum filtration to give the title compound as a very pale yellow powder (0.042 g, 31%): mp 177.5-180.8 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.89 (s , 1H), 7.44 (s, 1H), 7.41 (d, 1H, J = 8.3Hz), 6.99 (d, 1H, J = 8.3Hz), 5.80 (q, 1H, J = 7.3 Hz), 4.59 (s, 2H). FABLRMS m / z 275 (M + H). EIHRMS m / z 274.0417 (M < + >, 274.0453). Analytical Calcd for C 12 H 9 F 3 O 4 : C, 52.57; H, 3.31. Found: C, 52.43; H, 3.34. Example 81 6- (difluoromethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl 6- (difluoromethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate. Ethyl 6-formyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylate (Example 75, step 1) (1.672 g, 5.569 mmol) in methylene chloride (1.5 mL) was added to methylene chloride (1.5 mL). And diethylaminosulfa trifluoride (DAST) (0.74 mL, 0.898 g, 5.569 mmol) were added in an injector for greater than 0.07 h. After stirring for 20 hours, the reaction was stirred in aqueous HCL (2.0N) and the mixture was extracted with diethyl ether. The ether phase was washed with dilute aqueous HCl (2.0N), saturated NaHCO 3 solution, brine, dried over MgSO 4, filtered and concentrated in vacuo to give a colorless transparent fat. The fats and oils are ethyl-6-difluoromethyl-2-trifluoromethyl-2H-1-benzopyran-3, which is a solidified fat that is purified by flash chromatography (silica gel 60, (5: 1; hexanes: ethyl acetate). .-carboxylate (0.96g, 54%) to give the product the material was suitable purity for use without further purification in the next step: 1 H NMR (genus tone -d 6/300 MHz) 7.97 ( s , 1H), 7.74 (s, 1H), 7.65 (d, 1H, J = 8.5 Hz), 7.18 (d, 1H, J = 8.5 Hz), 6.90 (t, 1H, J = 56.0 Hz), 5.94 (q , 1H, J = 7.0 Hz, 4.40-4.25 (m, 2H), 1.34 (t, 3H, J = 7.0 Hz). Step 2. Preparation of 6- (Difluoromethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid. Aqueous NaOH (1.31 mL, 3.277 mmol, 2.5 M solution) was added to the ester (step 1) (0.880 g, 2.731 mmol) in THF: EtOH: H 2 O (7: 2: 1, 10 mL). The resulting solution was stirred for 60 hours. The reaction compound was partially concentrated in vacuo to remove organic solvent and diluted with H 2 O. The resulting aqueous solution was washed with diethyl ether and nitrogen was introduced to remove the ether and acidified with concentrated hydrochloric acid. The resulting oleaginous suspension was extracted with diethyl ether. The combined organic phases were dried over MgSO 4 , filtered in vacuo and concentrated to afford the title compound (0.438 g, 60%) as a solid that solidified to white crystals: mp 134.7-136.2 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.97 (s , 1H), 7.73 (s, 1H), 7.67 (dd, 1H, J = 8.5, 1.0Hz), 7.17 (d, 1H, J = 8.5Hz) , 6.89 (t, 1H, J = 56.2 Hz), 5.90 (q, 1H, J = 7.1 Hz). FAB-ESLRMS m / z 293 (M−H). EIHRMS m / z 293.0235 (M−H, calculated 293.0237). Analytical Calcd C 12 H 7 F 5 O 3 : C, 49.00; H, 2.40. Found: C, 48.78; H, 2.21. Example 82 2,6-bis (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl 2.6-bis (trifluoromethyl) -4-oxo-H-1-benzopyran-3-carboxylate. Aqueous sodium hydride (0.971 g, 22.07 mmol of 60% fat-dispersed reactant) was stirred in toluene (100 mL) with ethyl 4,4,4-trifluoroacetoacetate (3.22 mL, 4.06 g, 22.07 mmol). To the solution. After gas evolution, 2-fluoro-5- (trifluoromethyl) benzoyl chloride (5.00 g, 22.07 mmol) was added. The reaction was stirred at rt for 24 h and then heated to 105 ° C. for 24 h. After cooling to room temperature, the reaction was diluted with diethyl ether and the resulting solution was washed with H 2 O and brine, dried over MgSO 4 , filtered in vacuo and concentrated to give a slightly sticky white solid. This solid was triturated with hexane to afford the required ester of white powder (3.05 g, 39%): mp 116-120.1 ° C. 1 H NMR (CDCl 3 / 300MHz ) 8.52 (d, 2H, J = 1.6Hz), 8.03 (dd, 1H, J = 8.9, 2.2Hz), 7.71 (d, 1H, J = 8.9Hz), 4.48 (q , 2H, J = 7.3 Hz), 1.39 (t, 3H, J = 7.3 Hz). FABLRMS m / z 355 (M + H). Analytical Calculations C 14 H 8 F 6 O 4 : C, 47.45; H, 2.28. Found: C, 47.59; H, 2.43. Step 2. Preparation of ethyl 2.6-bis (trifluoromethyl) -4-oxo-dihydrobenzopyran-3-carboxylate. Ethyl 2.6-bis (trifluoromethyl) -benzopyran-4-one-3-carboxylate (step 1) (2.307 g, 6.513 mmol) and THF (20 mL) were added to a 250 mL round bottom flask to give a pale yellow solution. Ethanol (20 mL) is added and the reaction is cooled in an ice-salt electrolyzer. While maintaining the reaction temperature below 9 ℃, NaBH 4 (0.246g, 6.513mmol) was added in two portions and the mixture was stirred for one hour. The intact reaction mixture was poured into a stirred mixture of ice (200 mL) and concentrated hydrochloric acid (12N, 2 mL) to give a precipitate. Vacuum filtration of the resulting suspension gave the desired keto ester (2.204 g, 87%) as a pale pink powder, which was of a suitable purity for use in the next step without further purification: mp 71.8-76.9 ° C. 1 H NMR (acetone -d 6/300 MHz) 12.71 ( br s, 1H exch), 8.01 (d, 1H, J = 2.0Hz), 8.01 (d, 1H, J = 2.0Hz), 7.88 (dd, 1H , J = 8.7, 1.8 Hz), 7.31 (d, 1H, J = 8.7 Hz), 5.98 (q, 1H, J = 6.6 Hz), 4.51-4.28 (m, 2H), 1.35 (t, 3H, J = 7.0 Hz). FABLRMS m / z 355 (MH). ESHRMS m / z 355.0394 (M−H, calculated 355.0405). Analytical Calcd C 14 H 10 F 6 O 4 : C, 47.21; H, 2.83. Found: C, 47.31; H, 297. Step 3. Preparation of ethyl 2.6-bis (trifluoromethyl) -4-trifluoromethanesulfonato-2H-1-benzopyran-3-carboxylate. Attach a funnel to a 50 mL three-neck molton flask, place it in two stoppers with 2-6-di-tert-butylpyridine (1.576 g, 1.50 mmol) and methylene chloride (12 mL) and inject trifluoromethanesulfonic hydride with an injector (1.08 mL, 1.80 g, 1.25 mmol) was added. To the solution was added dropwise a solution of a keto ester of methylene chloride (10 mL) (step 2) (1.822 g, 5.115 mmol) for 0.33 hours and the reaction was stirred for 48 hours. The resulting almost white suspension was placed in a 100 mL round bottom flask and concentrated in vacuo. The remainder was suspended in diethyl ether (50 mL) and vacuum filtered to remove salt. The filtrate was further diluted with diethyl ether (50 mL), washed with ice-cold HCl solution (2N), brine, dried over Na 2 CO 3 , filtered and concentrated in vacuo to be used in the next step without further purification. The required triflate (1.64G, 66%) was obtained as a powder of brown lumps of appropriate purity. Step 4. Preparation of ethyl 2,6-bis (trifluoromethyl) -2H-1-benzopyran-3-carboxylate. LiCl (0.136g, 3.219mmol) was added to a 25mL pair flask and fixed in a high vacuum state and heated with a radiator to remove moisture from the surface. After cooling the flask to room temperature, tetrakis (triphenylphosphine) palladium (O) (0.124 g, 0.10 mmol) and THF (2 mL) were added. The flask was fixed with a reflex condenser and the apparatus was washed with nitrogen. THF (2 mL) triflate solution (step 3) (0.524 g, 1.073 mmol) and tri-n-butyltin hydride (0.32 mL, 0.34 g, 1.18 mmol) were added sequentially by injector. The resulting pale orange solution was heated to 50 ° C. with stirring for 1 h, heated to 60 ° C. for 1 h and 65 ° C. for 1 h. After the reaction was cooled to room temperature, 2N HCl was added, stirred, and extracted with hexane. The hexane phase was dried over MgSO 4 , filtered and concentrated to give a pale brown oil. The fats and oils were dissolved in hexanes and washed with an aqueous ammonium fluoride solution. The resulting hexane phase was dried over MgSO 4 , filtered and concentrated in vacuo to give a solid, pale yellow oily solid that was a flake powder (0.443 g). The solid was purified by flash silica chromatography (adsorbent: hexane-methylene chloride, 4: 1) to afford ethyl 2,5-di-trifluoromethyl-2H-1 of white crystals of appropriate purity to proceed to the next step. -Benzopyran-3-carboxylate (0.069 g, 19%) was obtained. Step 5. Preparation of 2,6-bis (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid. A stirred solution of the ester (step 4) (0.065 g, 0191 mmol) in THF-EtOH-H 2 O (7: 2: 1, 1 mL) was added to NaOH solution (0.084 mL, 0.210 mmol) at room temperature and then stirred overnight. It was. The reaction was partially concentrated in vacuo to give a pale clear yellow syrup. The syrup was diluted with water (5 mL) and brine (1 mL) and washed with diethyl ether (3x5 mL). The resulting aqueous phase was injected with nitrogen to remove ether. While stirring, concentrated HCl was added to the aqueous phase to give a very fine white precipitate. The suspension was extracted with diethyl ether, the ether was dried over Na 2 SO 4 , filtered and concentrated by slow evaporation at atmospheric pressure. The result is a mixture of hexane and ethyl lactate genus recrystallized to give the compound (0.038g, 64%) of the title fine brown powder: mp 143.5-145.2 ℃, 1 H NMR ( acetone -d 6/300 MHz) 11.97-11.67 ( br s, 1H), 8.03 (s, 1H), 7.92 (s, 1H), 7.77 (d, 1H, J = 8.5 Hz), 7.26 (d, 1H, J = 8.7 Hz), 5.96 (q, 1H, J = 7.0 Hz). FABLRMS m / z 311 (MH). ESHRMS m / z 311.0107 (M−H, calculated 311.0143). Example 83 5,6,7-trichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid The 3,4,5-trichlorophenyl was converted to 3-ethoxysalicylaldehyde in a similar procedure to Example 11, Step 1 above. Raised to 4,5,6- trichloroethane room aldehyde was converted to the title compound by a similar procedure as in Example 1: 1 H NMR (acetone -d 6/300 MHz) 8.05 ( s, 1H), 7.40 (s , 1H), 5.99 (q, 1H, J = 7.0 Hz). ESLRMS m / z 345 (MH). ESHRMS m / z 344.9113 (M−H, calculated 344.9100). Analytical calculation C 11 H 4 Cl 3 F 3 O 3 + 0.89 wt% H 2 O: C, 37.68; H, 1.25; Cl, 30.33. Found: C, 37.48; H, 1.25; Cl, 30.33. Example 84 6,7,8-trichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2,3,4-trichlorophenyl was converted to 3-ethoxysalicyl aldehyde in a similar procedure to Example 11, Step 1 above. The 3,4,5-trichlorosalicyl aldehyde was converted to the title compound in a similar procedure to Example 1 above: mp 222.0-225.3 ° C. 1 H NMR (acetone -d 6/300 MHz) 7.94 ( s, 1H), 7.78 (s, 1H), 6.07 (q, 1H, J = 7.0Hz). ESLRMS m / z 345 (MH). EIHRMS m / z 344.9117 (M−H, calculated 344.9100). Analytical Calcd C 11 H 4 Cl 3 F 3 O 3 + 1.56 wt% H 2 O: C, 37.43; H, 1. 32; Cl, 30.13. Found: C, 37.79; H, 0.93; Cl, 29.55. Example 85 7-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 3-ethylphenyl was converted to the title compound in a similar procedure as in Example 2 above: mp 167.0-168.6 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.84 (s, 1H), 7.15 (d, 1H, J = 7.5Hz), 6.84 (m, 2H), 5.66 (q, 1H, J = 6.8Hz), 2.63 (q , 2H, J = 7.7 Hz, J = 7.7 Hz), 1.24 (t, 3H, J = 7.7 Hz). Analytical Calculations C 13 H 11 F 3 O 3 : C, 57.36; H, 4.07. Found: C, 57.25; H, 4.10. Example 86 6- (methylsulfinyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl-6- (methylsulfonyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate. Ethyl 6- (methylthionone) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate of methylene chloride (Example 2, step 2) (1.014 g, 3.18 mmol) to -50 ° C Cooled. (Dry ice acetone) While stirring, meta-chloroperbenzoic acid (0.91 g of 60% reactant, 3.18 mmol) was added and reacted for 3 hours. Aqueous NaHSO 3 solution (40 mL 0.25 M) was added to the reaction. More methylene chloride was added and the phases were mixed and separated. The organic phase was washed with aqueous NaHSO 3 solution, aqueous saturated NaHSO 3 solution, brine, dried over MgSO 4 , filtered and concentrated to give an oil. The oil was diluted with isoacetone (2 mL) and concentrated to give a crystallized oil. Hexane was added and the solution was heated and methylene chloride was added until partial dissolution occurred. After cooling overnight, the suspension was vacuum filtered to give sulfoxide saturated ethyl ether (0.735 g, 71%) as white acicular crystals: mp 92.2-98.4 ° C. The ester is of sufficient purity to be used without further purification. Step 2. Preparation of 6- (methylsulfinyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxy hour. The ester solution (Step 1) (0.683 g) of THF: EtOH: H 2 O (7: 2: 1, 4 mL) was stirred and aqueous NaOH solution (0.98 mL of 2.5 M, 2.45 mmol) was added. After stirring for 12 hours, the reaction was partially concentrated in vacuo to remove the organic solvent. The remainder was diluted with water, washed with diethyl ether, injected with nitrogen to remove diethyl ether, and acidified with concentrated hydrochloric acid to obtain an oily suspension. The suspension was extracted with diethyl ether and the resulting organic phase was dried over MgSO 4 , filtered and diluted with hexanes. When concentrated in vacuo, the title acid is obtained as a sticky white powder (0.425 g, 68%): mp 148.3-151.0 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.99 (s , 1H), 7.82 (s, 1H), 7.78-7.68 (m, 1H), 7.24 (d, 1H, J = 8.3Hz), 5.92 (q, 1H, J = 7.1 Hz), 2.73 (s, 3H). FABLRMS m / z 307 (M + H). ESHRMS m / z 305.0098 (M−H, calculated 305.0095). Analytical Calculations C 12 H 9 F 3 O 4 S 1 : C, 47.06; H, 2.96; S, 10.47. Found: C, 46.69; H, 2. 86; S, 10.45. Example 87 5,8-dichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2,5-dichlorophenyl was converted to 3,6-dichlorosalicylaldehyde in a similar procedure to Example 2, Step 1 above. 3,6-Dichlorosalicylaldehyde was converted to the title compound in a similar manner to Examples 11, 2 and 3 above: mp 205.7-207.1 ° C. 1 H NMR (acetone -d 6/300 MHz) 8.02 ( s, 1H), 7.53 (d, 1H, J = 8.7Hz), 7.22 (d, 1H, J = 8.7Hz), 6.04 (q, 1H, J = 7.1 Hz). FABLRMS m / z 311 (MH). ESHRMS m / z 310.9506 (MH, calculated 310.9490). Analytical Calcd C 11 H 5 Cl 2 F 3 O 3 + 0.63 wt% H 2 O: C, 41.94; H, 1.67. Found: C, 41.54; H, 1.27. Example 88 6- (pentafluoromethyl) -2- (trifluoroethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl 6- (pentafluoroethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate. Potassium pentafluoro propionate (0.476 g, 2.35 mmol) was dissolved in toluene (6 mL) and DMF (6 mL). The vessel was fixed in the distillation section and CuI (0.471 g, 2.474 mmol) was added with stirring. The reaction was heated to 120 ° C. and toluene was removed by distillation. Ethyl 6-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 72, step 3) (0.469 g, 1.178 mmol) was added and the reaction was brought to 150 ° C. for 2 hours. Heated. The reaction was cooled to room temperature and then separated with diethyl ether and H 2 O. The organic phase was dried over MgSO 4 , filtered and concentrated in vacuo. The remainder of the result is purified by flash chromatography (silica gel 60, adsorbent: hexane-ethyl acetate, 8: 1), and the solution is concentrated to give the required ester as a brown solid mass suitable for use without further purification (0.096 96, 21%). was obtained: 1 H NMR (acetone -d 6/300 MHz) 8.04 ( s, 1H), 7.91 (d, 1H, J = 2.2Hz), 7.74 (dd, 1H, J = 8.7, 2.2Hz), 6.00 ( q, 1H, J = 7.1 Hz, 4.42-4.24 (m, 2H), 1.34 (t, 3H, J = 7.3 Hz. Step 2. Preparation of 6- (pentafluoroethyl) -2- (trifluoromethyl) -2-1-benzopyran-3-carboxylic acid. Ethyl ether solution (step 1) (0.090 g, 0.231 mmol) was stirred in THF: EtOH: H 2 O (7: 2: 1) (4 mL), and aqueous NaOH solution (0.11 mL, 2.5 M) was added thereto. After stirring for 16 hours, the reaction was partially concentrated in vacuo to remove the organic solvent, diluted with H 2 O and washed with diethyl ether. The resulting aqueous phase was acidified with concentrated hydrochloric acid to extract diethyl ether, dried over MgSO 4 , filtered and concentrated in vacuo to give a fat or oil. The oil was purified by flash chromatography (silica, hexane-ethyl acetate, 3: 1 and 5% acetic acid). This process afforded the title acid (0.020 g, 24%) as a white powder: mp 162.3-164.7 ° C. 1 H NMR (acetone -d 6/300 MHz) 8.05 ( s, 1H), 7.90 (s, 1H), 7.74 (d, 1H, J = 8.7Hz), 7.29 (d, 1H, J = 8.7Hz), 5.97 (q, 1H, J = 6.8 Hz). FABLRMS m / z 361 (MH). ESHRMS m / z 361.0111 (MH, calculated 361.0094). Example 89 6- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 4-tert-butylphenol was converted to the title compound in a similar manner as in Example 2 above: mp 170.6-173.2 ° C. 1 H NMR (acetone -d 6/300 MHz) 7.89 ( s, 1H), 7.5-7.4 (m, 2H), 6.93 (d, 1H, J = 8.4Hz), 5.76 (q, 1H, J = 7.2Hz ), 1.3 (s, 9H). Analytical Calculations C 15 H 15 O 3 F 3 : C, 60.00; H, 5.04. Found: C, 59.93; H, 5.12. Example 90 5- (hydroxymethyl) -8-methyl-2- (trifluoromethyl) -2H-pyrano [2,3-C] pyridine-3-carboxylic acid 3-hydroxymethyl-5-methyl-4-formylpyridine was converted to the title compound in a similar manner to Example 1 above: mp 76.1-80.1 ° C. 1 H NMR (acetone -d 6/300 MHz) 8.15 ( s. 2H), 5.93 (q, 1H, J = 7.2Hz), 1.3 (s, 9H) 5.30 (br s, 1H), 4.79 (br s, 1H), 2.41 (s, 3H). ESHRMS m / z 288.0485 (M + H, calculated 288.0483). Example 91 2- (trifluoromethyl) -6-[(trifluoromethyl) thio] -2H-1-benzopyran-3-carboxylic acid 4- (trifluoromethoxy) phenol in a procedure similar to Example 2, Step 1, above 5- (trifluoromethoxy) salicylaldehyde in a procedure similar to Examples 11, Steps 2 and 3, to the title compound Converted: mp 139.1-143.2 ° C. 1 H NMR (acetone -d 6/300 MHz) 7.95 ( s. 1H), 7.88 (d, 2H, J = 2.4Hz), 7.71-7.75 (m, 1H), 6.93 (d, 1H, J = 8.7Hz ), 5.91 (q, 1H, J = 6.9 Hz). Analytical Calcd C 12 H 6 O 3 F 3 S: C, 41.87; H, 1.76. Found: C, 41.94; H, 1.84. Example 92 6- (trifluoromethyl) -6H-1,3-dioxolo [4.5-g] [1] benzopyran-7-carboxylic acid. 4-tert-butylphenol was converted to the title compound in a similar manner as in Example 2 above: mp 245.8-247.8 ° C. 1 H NMR (acetone -d 6/300 MHz) 7.77 ( s. 1H), 6.95 (s, 1H), 6.12 (s, 1H), 6.05 (d, 2H, J = 0.90Hz), 5.91 (q, 1H , J = 7.2 Hz). Analytical Calcd C 12 H 7 O 3 F 3 : C, 50.01; H, 2.45. Found: C, 50.02; H, 2.50. Example 93 8-ethoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 2-ethoxyphenyl was converted to 3-ethoxysalicylaldehyde in a similar procedure as in Example 11. 3-Ethoxysalicylaldehyde was converted to the title compound in a similar manner to Example 1 above: mp 159.4-160.9 ° C. 1 H NMR (acetone -d 6/300 MHz) 7.86 ( s. 1H), 6.97-7.14 (m, 3H), 5.83 (q H-F '1H, J = 7.2Hz), 4.12 (q, 2H, J = 7.2 Hz), 1.38 (t, 3H, J = 7.2 Hz). FABLRMS m / z 289.0656 (M + H, calculated 289.0686). Analytical Calcd C 11 H 11 F 3 O 4 : H, 3.85. Found: C, 54.06; H, 3.83. Example 94 6-chloro-2,7-bis (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 4-Chloro-3- (trifluoromethyl) phenyl was converted to the title compound in a similar manner to Example 11 above: mp 180.9-182.4 ° C. 1 H NMR (acetone -d 6/300 MHz) 7.96 ( s, 1H), 7.84 (s, 1H), 7.47 (s, 1H), 5.96 (q, 1H, J = 6.8Hz), 2.50 (s, 3H ). FABLRMS m / z 345 (M−H). FABHRMS m / z 344.9767 (M−H, calculated 344.9753). Analytical Calcd C 12 H 5 ClF 6 O 3 : C, 41.58; H, 1. 45; Cl, 10.23. Found: C, 41.57; H, 1.50; Cl, 10.33. Example 95 5-methoxy-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 6-methoxysalicylaldehyde was converted to the title compound in a procedure similar to Example 11, steps 2 and 3 above: mp 204.5-206.7 ° C. 1 H NMR (acetone -d 6/300 MHz) 8.08 ( s, 1H), 7.38 (dd, 1H, J = 8.5Hz 8.3Hz), 6.74 (d, 1H, J = 8.5Hz), 6.65 (d, 1H , J = 8.3 Hz), 5.80 (q, 1H, J = 7.2 Hz), 3.94 (s, 3H). FABLRMS m / z 273 (MH). EIHRMS m / z 274.0444 (M < + >, 274.0453). Analytical Calcd C 12 H 9 F 3 O 4 : C, 52.57; H, 3.31. Found: C, 52.47; H, 3.34. Example 96 6-benzoyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Ethyl-6-benzoyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate. Ethyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 10, Step 1) (1.59 g, 5.8 mmol) was dissolved in 1,2-dichloroethane (3 mL), A 0 ° C. suspension of aluminum chloride (2.59 g, 19.4 mmol) added to 1,2-dichloroethane (3 mL) was added. A solution of benzoyl chloride (1.01 g, 7.2 mmol) in 1,2-dichloroethane (3 mL) was added and the reaction was heated to 80 ° C. and stirred for 4 h. The solution was poured into 3N HCl and ice and extracted with ethyl acetate. Once the ethyl acetate phases were combined, washed with 3N HCl, saturated sodium bicarbonate, brine, dried over MgSO 4 and concentrated in vacuo. The ester was purified by flash chromatography on silica gel (1: 9 ethyl acetate with hexane in fluid) to yield an ester which was a white crystalline solid (0.26 g, 12%): mp 114.7-116.1 ° C. 1 H NMR (CDCl 3/300 MHz) 7.82 (dd, 1H, J = 8.5Hz 2.0Hz), 7.76 (m, 4H), 7.61 (m, 1H), 7.50 (m, 2H), 7.09 (d, 1H , J = 8.7 Hz), 5.79 (q, 1H, J = 6.8 Hz), 4.34 (m, 2H), 1.36 (t, 3H, J = 7.2 Hz). Step 2. Preparation of 6-benzoyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid. The ester (0.24 g, 0.64 mmol) obtained in step 1 was dissolved in THF (2 mL) and ethanol (2 mL), treated with 2.5N sodium hydroxide (1.5 mL, 3.8 mmol) and stirred at room temperature for 4.3 hours. The reaction was concentrated in vacuo and then acidified with 3N HCl to yield a solid. The solid was filtered and recrystallized with ethanol-water to yield a white solid (0.14 g, 64%): mp 269.8-270.8 ° C. 1 H NMR (acetone -d 6/300 MHz) 8.04 ( s, 1H), 7.99 (d, 1H, J = 2.0Hz), 7.88 (dd, 1H, J = 8.5Hz 2.0Hz), 7.79 (m, 2H ), 7.68 (m, 1H), 7.57 (m, 1H), 7.23 (d, 1H, J = 8.6 Hz), 5.98 (q, 1H, J = 7.0 Hz). FABLRMS m / z 347 (MH). ESHRMS m / z 347.0560 (M−H, calculated 347.0531). Analytical Calculations C 18 H 11 F 3 O 4 : C, 62.08; H, 3.18. Found: C, 61.48; H, 3.22. Example 97 6- (4-chlorobenzoyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was calculated by a procedure similar to Example 96 above: mp 268.3-269.4 ° C. 1 H NMR (acetone -d 6/300 MHz) 8.03 ( s, 1H), 7.99 (d, 1H, J = 2.0Hz), 7.89 (dd, 1H, J = 8.5Hz, 2.0Hz), 7.81 (d, 2H, J = 8.5 Hz, 7.62 (d, 2H, J = 8.5 Hz), 7.23 (d, 1H, J = 8.5 Hz), 5.98 (q, 1H, J = 7.1 Hz). FABLRMS m / z 381 (MH). ESHRMS m / z 381.0135 (M−H, calculated 381.0141). Analytical Calcd C 18 H 10 ClF 3 O 4 : C, 56.49; H, 2.63; Cl, 9.26. Found: C, 56.35; H, 2. 66; Cl, 9.34. Example 98 6- (4-hydroxybenzoyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was calculated by a procedure similar to Example 96 above: mp 234.0-239.5 ° C. 1 H NMR (acetone -d 6 / 300MHz) 8.03 (s , 1H), 7.92 (d, 1H, J = 2.0Hz), 7.83 (dd, 1H, J = 8.5Hz 2.0Hz), 7.74 (d, 2H, J = 8.7 Hz), 7.20 (d, 1H, J = 8.5 Hz), 7.00 (d, 1H, J = 8.7 Hz), 5.94 (q, 1H, J = 7.1 Hz). ESHRMS m / z 363.0471 (MH, calculated 363.0480). Example 99 6-phenoxy-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 4-phenoxyphenol was converted to 5-phenoxysalicylaldehyde in a procedure similar to Example 2, Step 1 above. 5-phenoxysalicylaldehyde was converted to the title compound in a procedure similar to Examples 11, 2 and 3 above: mp 184.9-186.4 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.90 (s , 1H), 7.39 (m, 2H), 7.20 (d, 1H, J = 2.0Hz), 7.08 (m, 3H), 7.02 (m, 2H) , 5.98 (q, 1H, J = 7.2 Hz). FABLRMS m / z (MH). FABHRMS m / z 337.0663 (M + H, calculated 337.0687). Analytical Calcd C 17 H 11 F 3 O 4 : C, 60.72; H, 3.30. Found: C, 60.62; H, 3.29. Example 100 8-chloro-6- (4-chlorophenoxy) -2-trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of 5-phenoxysalicylaldehyde. Ethyl magnesium bromide (67.5 mL, 202.5 mmol of approximately 3.0 M solution in diethyl ether) was added to toluene (50 mL). A solution of 4-phenoxyphenol (25.00 g, 134.26 mmol) in diethyl ether (35 mL) was added to generate a gas. The reaction was heated to 80 ° C. for distillation of diethyl ether. Toluene (300 mL), HMPA (23.4 mL, 24.059 g, 134.26 mmol) and paraformaldehyde (10.07 g, 335.65 mmol) were added and the reaction was heated to 85 ° C. for 4 hours. The reaction was cooled to room temperature and acidified with 2N HCl. The resulting phase was separated to give an organic phase. The organic phase was washed with brine. The combined aqueous phase was extracted with methylene chloride. The organic phases were combined, dried over MgSO 4 , filtered and concentrated in vacuo to yield a yellow oil. The oil was purified by silica flash chromatography (hexane-ethyl acetate, 95: 5). Vacuum concentration of the required portion yielded salicylate of pale yellow powder (12.0 g, 42%) of sufficient purity for use in the next step. Step 2. Preparation of 3-chloro-5- (4-chlorophenoxy) salicylaldehyde. After stirring salicylic aldehyde (step 1) (0.981 g, 4.58 mmol) in acetic acid (20 mL), chlorine gas was added to the tube until the yellow color of chlorine continued. After stirring for 4 hours at room temperature the reaction was treated with nitrogen and diluted with water (50 mL). The resulting oily suspension was extracted with methylene chloride. The methylene chloride phase is washed with sodium bisulfite solution, dried over MgSO 4 , filtered and concentrated in vacuo, with two chlorine of yellow oil (0.66 g, 51%) of sufficient purity to be used without further purification in the next step. Substituted salicyaldehyde was calculated. Step 3. Preparation of ethyl-8-chloro-6- (4-chlorophenoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate. Salicyaldehyde substituted with two chlorine (step 2) (0.66 g, 2.3 mmol), triethylamine (0.49 g, 4.8 mmol), ethyl-4,4,4-trifluorocrotonate (0.59 g, 3.5 mmol) was added to dimethyl sulfoxide (5 mL) and heated to 85 ° C. for 3.5 h, the reaction was cooled to room temperature and diluted with ethyl acetate (50 mL). The resulting mixture was washed with 3N HCl (50 mL), aqueous potassium carbonate solution (10 wt%, 2 × 30 mL) and brine. The organic phase was dried over MgSO 4 , filtered in vacuo and concentrated to yield a brown oil. The oil was purified by flash silica chromatography (hexane-ethyl acetate, 9: 1) to give substituted 2H-1-benzopyran (0.39 g, 39%) of sufficient purity for use without further purification in the next step. Calculated. Step 4. Preparation of 8-chloro-6- (4-chlorophenoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid. A solution of ethanol-THF (4 mL, 1: 1) and substituted 2H-1-benzopyran ethyl ester (step 3) (0.37 g, 0.85 mmol) was added sodium hydroxide solution (2 mL of 2.5 N, 5 mmol). After stirring for 6 hours, the mixture was concentrated in vacuo. The mixture was acidified with 3N HCl and vacuum filtered to give a solid. This solid was recrystallized from ethanol-water to give the title mixture of yellow crystals (0.134 g, 38%): mp 227.8-228.9 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.93 (s , 1H), 7.42 (d, 2H, J = 8.9Hz), 7.24 (s, 2H), 7.12 (d, 2H, J = 8.9Hz), 5.97 (q, 1H, J = 7.1 Hz). FABLRMS m / z 403 (M−H). FABHRMS m / z 405.9790 (M + H, calculated 405.9801). Analytical Calcd C 17 H 9 Cl 2 F 3 O 4 + 2.33% H 2 O: C, 49.22; H, 2.45. Found: C, 49.19; H, 2.27. Example 101 2- (trifluoromethyl) -6- [4- (trifluoromethyl) phenoxy] -2h-1-benzopyran-3-carboxylic acid 4- (4-trifluoromethylphenyl) phenyl was converted to 5- (4-trifluoromethylphenyl) salicylaldehyde in a similar manner to Example 2, Step 1 above. 5- (4-Trifluoromethylphenyl) salicylaldehyde was subjected to a similar procedure to Examples 11, 2 and 3 above to yield the title compound: mp 153.5-154.4 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.91 (s , 1H), 7.71 (d, 2H, J = 8.9Hz), 7.33 (s, 1H, J = 2.8Hz), 7.15 (m, 4H), 5.86 (q, 1H, J = 7.1 Hz). FABLRMS m / z 403 (M−H). ESHRMS m / z 403.0399 (M−H, calculated 403.0405). Analytical Calcd C 18 H 10 F 6 O 4 : C, 53.48; H, 2.49. Found: C, 53.52; H, 2.55. Example 102 8- (1-methylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 4- (4-ethoxyphenyl) phenol was subjected to a similar procedure to Example 2 above to yield the title compound: mp 210.5-211.5 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.86 (s , 1H), 7.35 (d, 1H, J = 7.7z), 7.28 (s, 1H, J = 7.5Hz), 7.04 (t, 1H, J = 7.7 Hz), 5.85 (q, 1H, J = 7.2 Hz), 3.33 (sept, 1H, J = 7.1 Hz), 1.25 (d, 6H, J = 7.1 Hz). Analytical Calculations C 14 H 13 F 3 O 3 : C, 58.74; H, 4.58. Found: C, 58.65; H, 4.60. Example 103 6-chloro-8- (1-methylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 8- (1-Methylethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid (Example 6) was subjected to a similar procedure to Example 9 to yield the title compound: mp 185.4-189.2 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.87 (s , 1H), 7.38 (d, 1H, J = 2.4Hz), 7.34 (d, 1H, J = 2.4Hz), 5.90 (q, 1H, J = 7.3 Hz), 3.31 (m, 1 H), 1.24 (d, 6H, J = 6.8 Hz). Analytical Calcd C 15 H 14 ClF 3 O 3 : C, 52.43; H, 3.77; Cl, 11.05. Found: C, 52.58; H, 3.79; Cl, 10.96. Example 104 6- (4-Chlorophenoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was converted to 6-phenoxy-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid as a starting material through a process similar to that of Example 9. Calculated by: mp 140.5-142.5 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.90 (s , 1H), 7.39 (d, 2H, J = 9.1Hz), 7.25 (d, 1H, J = 2.6Hz) 7.01-7.15 (m, 4H), 5.85 (q, 1 H, J = 7.2 Hz). FABLRMS m / z 370 (M < + >). ESHRMS m / z 369.0130 (M−H, calculated 369.0141). Analytical Calcd C 17 H 10 ClF 3 O 4 + 0.96% H 2 O: C, 54.55; H, 2.80. Found: C, 54.38; H, 2.90. Example 105 8-chloro-2- (trifluoromethyl) -6- [4- (trifluoromethyl) phenoxy] -2H-1-benzopyran-3-carboxylic acid 2- (trifluoromethyl) -6- [4- (trifluoromethyl) phenoxy] -2H-1-benzopyran-3-carboxylic acid, in which the benzopyran-3-carboxylic acid was subjected to a procedure similar to that of Example 100 above. (Example 101) calculated as starting material: mp 223.7-226.0 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.94 (s , 1H), 7.74 (d, 2H, J = 8.5Hz), 7.35 (m, 2H), 7.25 (d, 2H, J = 8.5Hz), 6.00 (q, 1H, J = 7.0 Hz). FABLRMS m / z 437 (MH). ESHRMS m / z 437.0000 (MH, calculated 437.0015). Analytical Calcd C 18 H 9 ClF 6 O 4 : C, 49.28; H, 2.07; Cl, 8.08. Found: C, 49.42; H, 2. 12; Cl, 8.17. Example 106 3- (trifluoromethyl) -3H-benzofuro [3,2-f] [1] benzopyran-2-carboxylic acid. 2-hydroxydibenzofuran was converted to the title compound in a similar procedure to Example 2 above: mp 253.5-254.6 ° C. 1 H NMR (acetone -d 6 / 300MHz) 8.54 (s , 1H), 8.23 (d, 1H, J = 7.5Hz), 7.71 (s, 1H), 7.62 (m, 1H), 7.50 (m, 1H) , 7.23 (d, 1H, J = 8.9 Hz), 5.95 (q, 1H, J = 7.3 Hz). FABLRMS m / z 333 (M−H). ESHRMS m / z 333.0401 (M−H, calculated 333.0375). Analytical Calcd C 17 H 9 F 3 O 4 : C, 61.09; H, 2.71. Found: C, 60.95; H, 2.80. Example 107 6-chloro-8-cyano-2- (trifluoromethyl) -2H-1benzopyran-3-carboxylic acid Step 1. Preparation of ethyl-6-chloro-8- (hydroxyiminomethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate. Hydroxylamine hydrochloride (1.30 g, 18.7 mmol), sodium acetate (1.50 g, 19.4 mmol), and a mixture of ethanol-water (80:20, 15 mL) were stirred at room temperature for 0.4 h. Aldehyde (Example 76, Step 3) (3.07 g, 0.9 mmol) was dissolved in ethanol-water solution (4: 1, 25 mL) and added to the mixture and stirred at 100 ° C. for 1 h. The reaction was filtered hot and the filtrate was cooled to room temperature. The orange solid was crystallized in the filtrate obtained by vacuum filtration. The solid was dissolved in ethyl acetate, washed with water and brine, dried over MgSO 4 and concentrated in vacuo. The resulting solid was recrystallized from ethyl acetate-hexane to yield oxime (1.50 g, 47%) as a brown powder: mp 186.6-187.6 ° C. 1 H NMR (acetone -d 6 / 300MHz) 10.87 (s , 1H), 8.34 (s, 1H), 7.90 (s, 1H), 7.77 (d, 1H, J = 2.6Hz), 7.60 (d, 1H, J = 2.6 Hz), 6.02 (q, 1H, J = 7.1 Hz), 4.35 (m, 2H), 1.34 (t, 3H, J = 7.0 Hz). Step 2. Preparation of ethyl 6-chloro-8-cyano-2-trifluoromethyl-2H-1-benzopyran-3-carboxylate. Oxime (0.61 g, 1.7 mmol) and acetic anhydride (6 mL) of step 1 were stirred at 140 ° C. for 6.3 h. The reaction was poured into water, extracted with ethyl acetate, washed with saturated NaHCO 3 , brine, dried over MgSO 4 and concentrated in vacuo to yield a brown oil (1.09 g). The oil was purified by flash chromatography (10: 1; hexanes: ethyl acetate) to yield the title compound as a white solid (0.51 g, 88%); mp 114.6-115.6 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.65 (s, 1H), 7.53 (d, 1H, J = 2.4Hz), 7.44 (d, 1H, J = 2.4Hz), 5.87 (q, 1H, J = 6.4Hz ), 4.36 (m, 2H), 1.37 (t, 3H, J = 6.5 Hz). Step 3. Preparation of 6-chloro-8-cyano-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid. The ester of step 2 (0.51 g, 1.5 mmol) was dissolved in THF (5 mL) and ethanol (5 mL), treated with 2.5N sodium hydroxide and stirred at room temperature for 1.5 h. The reaction mixture was concentrated in vacuo, acidified with 3N HCl, extracted with ethyl acetate, washed with water, brine, dried over MgSO 4 , concentrated in vacuo and recrystallized with diethyl ether / hexane to give white powder (0.10 g, 21%) was calculated: mp 238.1-239.7 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.97 (s , 1H), 7.92 (d, 1H, J = 2.4Hz), 7.89 (d, 1H, J = 2.4Hz), 6.14 (q, 1H, J = 6.6 Hz). FABLRMS m / z 302 (MH), ESHRMS m / z 301.9819 (MH, calculated 301.9832). Analytical Calcd C 12 H 5 ClF 3 NO 3 : C, 47.47; H, 1.66; N, 4.61. Found: C, 47.41; H, 1.70; N, 4.55. Example 108 6-chloro-8 [(hydroxyimino) methyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was calculated from ethyl ether (Example 107, step 2) in a similar manner to Example 1, Step 2 above: mp 246.9-247.9 ° C. 1 H NMR (acetone -d 6 / 300MHz) 10.90 (brs , 1H), 8.35 (s, 1H), 7.92 (s, 1H), 7.78 (d, 1H, J = 2.6Hz), 7.61 (d, 1H, J = 2.6 Hz), 5.98 (q, 1H, J = 7.0 Hz). FABLRMS m / z 320 (MH). ESHRMS m / z 319.9959 (M−H, calculated 319.9937). Analytical Calcd C 12 H 7 ClF 3 NO 4 : C, 44.81; H, 2. 19; N, 4.35. Found: C, 44.92; H, 2. 25; N, 42.6. Example 109 6-chloro-8- (hydroxymethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was calculated using a carboxylic acid (Example 76, step 4) as a starting material, in a similar manner to Example 80: mp 174.6-178.9 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.90 (s , 1H), 7.57 (d, 1H, J = 2.6Hz), 7.47 (d, 1H, J = 2.6Hz), 5.87 (q, 1H, J = 7.0 Hz), 4.70 (s, 2H). FABLRMS m / z 309 (M + H). ESHRMS m / z 306.9981 (MH, calculated 306.9985). Analytical Calcd C 12 H 8 ClF 3 O 3 (3.81 wt.% H 2 O): C, 47.37; H, 3.08. Found: C, 47.33; H, 2.82. Example 110 8- (1H-benzimidazol-2-yl) -6-chloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl 8- (1H-benzimidazol-2-yl) -6-chloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate. A solution of nitrobenzene (20 mL), aldehyde (Example 76, step) (0.33 g, 0.99 mmol), 1,2-phenylenediamine (0.11 g, 1.02 mmol) was heated to 150 ° C. for 1.8 h. The reaction mixture was extracted with diethyl acetate, washed with brine, dried over MgSO 4 , concentrated in vacuo and purified by flash chromatography on silica gel (1: 9 with ethyl acetate, hexane as flow) and further purification. To yield an ester which is a brown solid (0.18 g, 43%) for use in the step. Step 2. Preparation of 8- (1H-benzimidazol-2-yl) -6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid. The ester of step 1 (0.18 g, 1.5 mmol) was dissolved in THF (5 mL) and ethanol (5 mL), treated with 2.5N sodium hydride (2.6 mL, 6.5 mmol) and stirred at room temperature for 1.7 h. The reaction mixture was concentrated in vacuo, acidified with 3N HCl, filtered and recrystallized from ethanol-water to yield a brown solid (0.09 g, 52%): mp> 300 ° C. 1 H NMR (acetone -d 6 / 300MHz) 8.59 (d , 1H, J = 2.6Hz), 8.03 (s, 1H), 7.73 (d, 1H, J = 2.6Hz), 7.67 (brs, 2H), 7.28 (m, 2H), 6.13 (q, 1H, J = 6.8 Hz). FABLRMS m / z 395 (M− { 37 Cl}). ESHRMS m / z 393.0262 (M−H, calculated 393.0254). Analytical Calcd C 18 H 10 ClF 3 N 2 O 3 (2.88 wt% H 2 O): C, 53.19; H, 2. 80; N, 6.89. Found: C, 53.22; H, 2. 90; N, 6.80. Example 111 7- (1,1-dimethylethyl) -2- (pentafluoroethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl 3-hydroxy-4,4,5,5-pentafluoropentanomate. Ethyl 4,4,5,5,5-pentafluoro-3-oxo-pentanoate (41.32 g, 0.18 mole) and diethyl ether (70 mL) solution were cooled to 0 ° C. and NaBH 4 (7.09 g, 0.19 mole) ). The reaction was warmed at rt and stirred for 2 h before treatment with 1N HCl (200 mL). The combined organic phases were washed with 1N HCl, brine, dried over MgSO 4 and concentrated in vacuo to yield hydroxy ester, a clear oil (46.40 g) to be used in the next step without further purification. Step 2. Preparation of ethyl 4,4,5,5,5-phennafluoro-2-pentenoate. The hydroxy ester of step 1 (46.40 g, 0.18 mole) was stirred with P 2 O 5 (25.59 g, 0.09 mole) at 120 ° C. for 2.6 hours and then vacuum distilled (95torr, 45-64 ° C.) to give a clear oil. (13.70g, 35%) were calculated: 1 H NMR (CDCl 3 / 300MHz) 6.78 (m, 1H), 6.57 (dt, 1H, J = 15.9Hz 2.0Hz), 4.30 (q, 2H, J = 7.3 Hz), 1.34 (t, 3H, J = 7.1 Hz). Step 3. Preparation of ethyl 7- (1,1-dimethylethyl) -2- (pentafluoroethyl) -2H-1-benzopyran-3-carboxylate. A mixture of 4-tert-butylsalicylaldehyde (Example 8, Step 1) (1.15 g, 6.4 mmol) and ethyl ester of Step 2 (1.59 g, 7.3 mmol) was dissolved in anhydrous DMF (4 mL). While stirring, K 2 CO 3 (1.10 g, 9.0 mmol) was added until light red. The reaction was stirred at rt for 100 h, acidified with 3N HCl, diluted with ethyl acetate, washed with saturated NaHCO 3 solution, brine, dried over MgSO 4 , filtered in vacuo and concentrated to give a brown oil. . The oil was calculated to 10% ethyl acetate / hexane as the adsorption, purification by flash chromatography on silica gel with the yellow five days (1.72g, 70%): 1 H NMR (CDCl 3 / 300MHz) 7.76 (s, 1H), 7.14 (d, 1H, J = 8.1 Hz), 7.04 (dd, 1H, J = 8.1 Hz 1.8 Hz), 6.94 (s, 1H), 5.92 (dd, 1H, J = 22.4 Hz 3.0 Hz), 4.32 (m , 2H), 1.35 (t, 3H, J = 7.2 Hz), 1.30 (s, 9H). Step 4. Preparation of 7- (1,1-dimethylethyl) -2- (pentafluoroethyl) -2H-1-benzopyran-3-carboxylic acid. The ester of step 3 (1.58 g, 4.20 mmol) was dissolved in THF (3 mL) and ethanol (3 mL), treated with 2.5N sodium hydroxide (2 mL, 5 mmol) and stirred at room temperature for 23.3 h. The reaction compound was concentrated in vacuo and acidified with 3N HCl to yield a suspension. Filtration gave a solid and recrystallized from ethanol-water to yield a yellow solid (0.76 g, 52%): mp 171.0-173.5 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.93 (s , 1H), 7.39 (d, 1H, J = 8.1Hz), 7.18 (dd, 1H, J = 8.1Hz 1.8Hz), 7.02 (s. 1H) , 6.01 (dd, 1H, J = 23.1 Hz 3.2 Hz), 1.32 (s, 9H). FABLRMS m / z 351 (M + H). EIHRMS m / z 350.0945 (M < + >, 350.0941). Analytical Calcd C 16 H 15 F 5 O 3 : C, 54.86; H, 4.32. Found: C, 54.88; H, 4.32. Example 112 6-chloro-8- (methoxymethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl 6-chloro-8- (hydroxymethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate. Aldehyde (Example 75, Step 1) (4.78 g, 14.3 mmol) The suspension was cooled to 0 ° C. and treated with NaBH 4 (0.33 g, 4.8 mmol). The solution was stirred for 10 min, treated with 3N HCl, extracted with ethyl acetate, washed with saturated NaHCO 3 , brine, dried over MgSO 4 and concentrated in vacuo to yield a brown solid (3.60 g, 75%) plug with silica gel the calculation was a brown solid was filtered through: 1 H NMR (CDCl 3 / 300MHz) 7.66 (s, 1H), 7.41 (d, 1H, J = 2.4Hz), 7.17 (d, 1H, J = 2.4Hz), 5.75 (q, 1H, J = 6.8 Hz), 4.71 (s, 2H), 4.33 (m, 2H), 1.85 (brs, 1H), 1.36 (t, 3H, J = 7.1). This solid was used in the next step without further purification. Step 2. Preparation of ethyl-6-chloro-8- (methoxymethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate. Alcohol (0.44 g, 1.3 mmol), silver triflate (0.36 g, 1.4 mmol) and 2.6-di-tert-butylpyridine (0.37 g, 1.9 mmol) from step 1 were added to methylene chloride (3 mL) cooled to 0 ° C. It was dissolved and treated with methyl iodine (0.40 g, 2.8 mmol). The reaction was warmed and stirred at rt for 4.6 h. The reaction was filtered through diatomaceous earth, the filtrate was washed with 3N HCl, saturated NaHCO 3 , brine, dried over MgSO 4 and concentrated in vacuo to yield a brown oil. This oil was adsorbed with 10% ethyl acetate-hexane to purify by flash chromatography on silica gel to yield the substituted 2H-1-benzopyran (0.19 g, 41%) which is a white oily solid suitable for use without further purification: 1 H NMR (CDCl 3 / 300MHz) 7.63 (s, 1H), 7.39 (d, 1H, J = 2.6Hz), 7.13 (d, 1H, J = 2.6Hz), 5.72 (q, 1H, J = 6.8Hz) , 4.44 (m, 2H), 4.30 (m, 2H), 3.41 (s, 3H), 1.85 (brs, 1H), 1.33 (t, 3H, J = 7.1). Step 3. Preparation of 6-chloro-8- (methoxymethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid. The ester of step 2 was hydrolyzed in a similar manner to Example 1, step 2: mp 166.7-168.0 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.90 (s , 1H), 7.50 (d, 1H, J = 2.6Hz), 7.46 (d, 1H, J = 2.4Hz), 5.92 (q, 1H, J = 7.1 Hz), 4.49 (s, 2H), 3.42 (s, 3H). FABLRMS m / z 321 (M−H). ESHRMS m / z 321.0141 (M−H, calculated 321.0141). Analytical Calcd C 13 H 10 ClF 3 O 4 : C, 48.39; H, 3.12. Found: C, 48.45; H, 3.11. Example 113 6-chloro-8- (benzyloxymethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was calculated by a procedure similar to Example 112 above: mp 133.8-135.4 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.90 (s , 1H), 7.54 (d, 1H, J = 2.6Hz), 7.51 (d, 1H, J = 2.4Hz), 7.42 (m, 5H), 5.91 (q, 1H, J = 7.1 Hz), 4.68 (s, 2H), 4.63 (s, 2H). FABLRMS m / z 399 (M + H). ESHRMS m / z 397.0454 (M−H, calcd 397.0461). Analytical Calcd C 19 H 13 ClF 3 O 4 : C, 57.23; H, 3.5 4; Cl, 8.89. Found: C, 57.34; H, 3.63; Cl, 8.77. Example 114 6-chloro-8-ethenyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethenyl-6-chloro-8-ethenyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate. Under N 2 in 100mL round bottom plastic disks ethyl 8-bromo-6-chloro-2-trifluoromethyl -2H- benzopyran-3-carboxylate (Example 74, Step 1) (2.21g, 5.73mmol) to It was dissolved in toluene (anhydrous solution 30mL). Tetrakis (triphenylphosphine) palladium (O) (0.132 g, 0.115 mmol) was added followed by tributylethyenylstannane (2.0 g, 6.31 mmol). The resulting solution was heated to reflux for 5 hours. The reaction mixture was cooled to room temperature and placed in 50 mL of 20% ammonium fluoride and stirred for 1 hour. Diethyl ether (100 mL) was added and the mixture was washed with water (2 × 50 mL). The organic phase was dried over MgSO 4 , filtered and evaporated to yield a yellow oil. The output was purified by flash chromatography (0.5% ethyl acetate in hexanes) to yield ester (0.86 g, 45%) as a yellow solid: mp 75.9-77.2 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.64 (s, 1H), 7.45 (d, 1H, J = 2.5Hz), 7.12 (d, 1H, J = 2.6Hz), 6.92 (dd, 1H, J = 17.7Hz , 11.3 Hz), 5.81 (d, 1H, J = 17.7 Hz), 5.76 (q, 1H, J = 6.8 Hz), 5.41 (d, 2H, J = 11.1 Hz), 4.36-4.29 (m, 2H), 1.36 (t, 3H, J = 7.3 Hz). FABLRMS m / z 350.1 (M + NH 4 + ). ESHRMS m / z 350.0796 (M + NH 4 + , calculated 350.0771). Analytical Calcd C 15 H 12 ClF 3 O 3 + 4.07% H 2 O): C, 51.95; H, 3.94. Found: C, 51.67; H, 3.69. Step 2. Preparation of 6-chloro-8-ethenyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid. Ester (step 1) (0.350 g, 1.05 mmol) was dissolved in a solution of THF: ethanol: water (7: 2: 1, 10 mL) and treated with sodium hydroxide (0.46 mL, 1.05 mmol) for 2.5 hours. Stirred at room temperature. The solvent was removed in vacuo and the remainder was dissolved in water (10 mL). Diethyl ether (10 mL) was added and the mixture acidified with concentrated hydrochloric acid. The phases were separated and the aqueous phase was extracted with diethyl ether (2x10 mL). The organic phases were combined, dried over MgSO 4 , filtered and evaporated to yield a yellow solid that was recrystallized from diethyl ether-hexane to yield the title compound as a yellow solid (0.288 g, 90%): mp 183.2-185.8 ° C. . 1 H NMR (CDCl 3 / 300MHz ) 7.77 (s, 1H), 7.49 (d, 1H, J = 2.2Hz), 7.16 (d, 1H, J = 2.4Hz), 6.93 (dd, 1H, J = 11.3, 17.7 Hz), 5.82 (d, 1H, J = 17.7 Hz), 5.74 (q, 1H, J = 6.9 Hz), 5.43 (d, 1H, J = 11.1 Hz). FABLRMS m / z 303 (MH). ESHRMS m / z 303.0014 (MH, calculated 303.003582). Analysis calculated C 13 H 8 ClF 3 O 3 + 1.58% H 2 O: C, 50.44; H, 2.78. Found: C, 50.42; H, 2.65. Example 115 6-chloro-8-ethynyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was calculated in a similar manner as in Example 114 above: mp 186.2-189.0 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.87 (s , 1H), 7.60 (d, 1H, J = 2.4Hz), 7.51 (d, 1H, J = 2.4Hz), 5.95 (q, 1H, J = 7.0 Hz), 4.02 (S, 1 H). FABLRMS m / z 301 (M−H). ESHRMS m / z 303.9875 (M−H, calculated 303.9879). Analytical Calcd C 13 H 6 ClF 3 O 3 : C, 51.59; H, 2.00; Cl, 11.71. Found: C, 51.26; H, 2.06; Cl, 11.40. Example 116 6-chloro-8- (2-thienyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was calculated in a similar manner as in Example 114 above: mp 257.5-258.8 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.91 (s , 1H), 7.79 (d, 1H, J = 2.4Hz), 7.74-7.72 (m, 1H), 7.62-7.61 (m, 1H), 7.51 ( d, 1H, J = 2.4 Hz, 7.19-7.16 (m, 1H), 6.04 (q, 1H, J = 7.1 Hz). FABLRMS m / z 359 (MH). ESHRMS m / z 358.9747 (M−H, calculated 358.9756). Analytical Calcd C 15 H 8 ClF 3 O 3 S: C, 49.94; H, 2. 24; C1, 9.83; S, 8.89. Found: C, 50.26; H, 2. 45; C1, 9.72; S, 9.00. Example 117 6-chloro-8- (2-furanyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was calculated in a similar manner to Example 114 above: mp 171.5-173.3 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.93 (s , 1H), 7.82 (d, 1H, J = 2.6Hz), 7.72-7.71 (m, 1H), 7.50 (d, 1H, J = 2.6Hz) , 7.16 (d, 1H, J = 2.4 Hz), 6.65-6.63 (m, 1H), 6.11 (q, 1H, J = 7.1 Hz). FABLRMS m / z 343 (MH). ESHRMS m / z 342.9995 (M−H, calc. 342.9985). Analytical Calcd C 15 H 8 ClF 3 O 4 + 1.31% H 2 O: C, 51.59; H, 2. 46; Cl, 10.15. Found: C, 51.57; H, 2. 33; Cl, 10.14. Example 118 6-chloro-8- (5-chloro-1-pentynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl-6-chloro-8- (5-chloro-1-pentenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate. Ethyl 6-chloro-iodo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylate (Example 73, step 2) (1.50 g, 3.47 mmol), tetrakis- (triphenylphosphine) Palladium (O) (0.2 g, 0.174 mmol), copper iodide (I) (0.066 g, 0.347 mmol) and triethylamine (1.05 g, 10.4 mmol) were dissolved in toluene (50 mL). 5-chloro-1-pentine (0.53 g, 5.20 mmol) was added by injector and the mixture was stirred at room temperature for 18 hours. The reaction was diluted with diethyl ether (50 mL) and the 0.5N HCl (2 × 25 mL) and water (2 × 25 mL) organic phases were dried over MgSO 4 , filtered and evaporated to yield an orange oil. The output was purified by flash chromatography using hexanes and 2% ethyl acetate. Recrystallization from hexanes gave the ester as a white solid (0.96 g, 68%): mp 84.8-85.9 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.61 (s, 1H), 7.33 (d, 1H, J = 2.6Hz), 7.14) d, 1H, J = 2.6Hz), 5.79 (q, 1H, J = 6.7Hz ), 4.37-4.29 (m, 2H), 3.75 (t, 2H, J = 6.7 Hz), 2.67 (t, 2H, J = 6.7 Hz), 2.11-2.03 (m, 2H), 1.35 (t, 3H, J = 7.2 Hz). FABLRMS m / z 424.1 (M + NH 4 + ). ESHRMS m / z 424.0694 (M + NH 4 + , calculated 424.0694). Analytical Calcd C 18 H 15 Cl 2 F 3 O 3 : C, 53.09; H, 3.71; Cl, 17.41. Found: C, 53.02; H, 3. 90; Cl, 17.63. Step 2. Preparation of 6-chloro-8- (5-chloro-1-pentynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid. Ester (step 1) (0.500 g, 1.23 mmol) was dissolved in THF-ethanol-water (7: 2: 1; 10 mL). It was treated with sodium hydroxide (0.49 mL, 1.23 mmol of 2.5N solution) and stirred for 18 hours at room temperature. The solvent was evaporated and the remainder dissolved in water (10 mL). Diethyl ether (10 mL) was added and the mixture was acidified with concentrated hydrochloric acid. The organic phase was separated and the aqueous phase extracted with diethyl ether (2x10 mL). The combined extracts were dried over MgSO 4 , filtered and evaporated to recrystallize with diethyl ether-hexane to give the title compound as a yellow solid (0.371 g, 80%): mp 154.4-156.4 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.88 (s , 1H), 7.53 (d, 1H, J = 2.4Hz), 7.44 (d, 1H, J = 2.4Hz), 5.94 (q, 1H, J = 7.1 Hz), 3.83 (t, 2H, J = 6.5 Hz), 2.68 (t, 2H, J = 6.8 Hz), 2.12-2.04 (m, 2H). ESLRMS m / z 377 (MH). ESHRMS m / z 376.9930 (M−H, calculated 376.9959). Analytical Calcd C 16 H 11 Cl 2 F 3 O 3 + 1.18% H 2 O: C, 50.08; H, 3.02; Cl, 18.48. Found: C, 50.11; H, 2.73; Cl, 18.28. Example 119 6-chloro-8- (1-pentenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was prepared in a similar manner to Example 118 above: mp 168.1-171.2 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.75 (s, 1H), 7.37 (d, 1H, J = 2.6Hz), 7.15 (d, 1H, J = 2.4Hz), 5.77 (1, 1H, J = 6.7Hz ), 2.44 (t, 2H, J = 6.9 Hz), 1.68-1.61 (m, 2H), 1.07 (t, 3H, J = 7.25 Hz). FABLRMS m / z 345 (M + H). ESHRMS m / z 343.0373 (M−H, calcd 343.0349). Analytical Calcd C 16 H 12 ClF 3 O 3 + 0.69% H 2 O: C, 55.36; H, 3.56. Found: C, 55.21; H, 3.62. Example 120 6-chloro-8- (phenylethynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was prepared by a similar procedure as in Example 118 above: mp 190.1-192.1 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.92 (s, 1H), 7.61-7.57 (m, 4H), 7.47-7.44 (m, 3H), 6.01 (q, 1H, J = 7.0Hz). ESLRMS m / z 377 (MH). ESHRMS m / z 377.167 (M−H, calculated 377.0192). Analytical Calcd C 19 H 10 ClF 3 O 3 : C, 60.26; H, 2. 66; Cl, 9.36. Found: C, 60.09; H, 2.73; Cl, 9.09. Example 121 6-chloro-8- (3,3-dimethyl-1-butynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was prepared in a similar manner to Example 118 above: mp 218.3-222.4 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.87 (s , 1H), 7.51 (d, 1H, J = 2.4Hz), 7.38 (d, 1H, J = 2.6Hz), 5.92 (q, 1H, J = 6.9 Hz), 1.32 (s, 9H). FABLRMS m / z 359 (M + H). ESHRMS m / z 357.0490 (M−H, calculated 357.0505). Analytical Calcd C 17 H 14 ClF 3 O 3 : C, 56.92; H, 3.93; Cl, 9.88. Found: C, 56.63; H, 3.94; Cl, 10.03. Example 122 6-chloro-8-[(4-chlorophenyl) ethynyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was prepared by a similar procedure as in Example 118 above: mp 210.4-211.4 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.75 (s, 1H), 7.48-7.43 (m, 3H), 7.36 (s, 1H), 7.33 (s, 1H), 7.22 (d, 1H, J = 2.6Hz) , 5.82 (q, 1H, J = 6.6 Hz). FABLRMS m / z 411 (MH). ESHRMS m / z 410.9802 (M−H, calculated 410.980259). Analytical Calcd C 20 H 12 C 12 F 3 O 3 : C, 55.23; H, 2. 20; Cl, 17.16. Found: C, 55.22; H, 2.07; Cl, 17.39. Example 123 6-chloro-8-[(4-methoxyphenyl) ethynyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was prepared in a similar manner to Example 118 above: mp 217.7-218.7 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.75 (s, 1H), 7.51-7.47 (m, 3H), 7.18 (d, 1H, J = 2.4Hz), 6.91-6.88 (m, 2H), 5.82 (1, 1H, J = 6.7 Hz). ESLRMS m / z 407 (MH). ESHRMS m / z 407.0293 (M−H, calculated 407.0298). Analytical Calcd C 20 H 12 ClF 3 O 4 : C, 58.77; H, 2.96; Cl, 8.67. Found: C, 58.68; H, 2. 85; Cl, 9.15. Example 124 6- (phenylethynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was substituted with ethyl-6-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 24, step 3) as starting material. Prepared in a similar manner to Example 118 above: mp 240.1-241.3 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.94 (s , 1H), 7.70-7.69 (m, 1H), 7.61-7.53 (m, 3H), 7.44-7.41 (m, 3H), 7.10 (d, 1H , J = 7.1 Hz). ESHRMS m / z 343.0550 (M−H, calcd 343.0582). Analytical Calculations C 19 H 11 F 3 O 3 : C, 66.29; H, 3.22. Found: C, 66.26; H, 3.29. Example 125 6-chloro-8- (4-chlorophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl 6-chloro-8- (4-chlorophenyl) -2-9trifluoromethyl) -2H-1-benzopyran-3-carboxylate. Ethyl 6-chloro-8-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 73, step 2) (1.3 g, 3.02 mmol), potassium carbonate (1.25 g , 9.06 mmol), 4-chlorophenylboric acid (0.52 g, 3.33 mmol) and tetrakis (triphenylphosphine) palladium (O) (0.174 g, 0.151 mmol) were added to toluene (30 mL) and the resulting solution was added. Heated to reflux for 18 hours. After cooling to room temperature the reaction compound was added to ethyl acetate (50 mL). It was washed with 1N HCl (2 × 25 mL), saturated aqueous sodium bicarbonate (2 × 25 mL) and water (2 × 25 mL). The organic phase was dried over MgSO 4 , filtered and concentrated in vacuo to yield a brown oil. The output was purified by flash chromatography using 1% ethyl acetate. Recrystallization with hexane yielded the ester as a white solid (0.79 g, 64%): mp 114.2-115.9 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.69 (s, 1H), 7.41 (s, 4H), 7.30 (d, 1H, J = 2.4Hz), 7.22 (d, 1H, J = 2.6Hz), 5.70 (1 , 1H, J = 6.9 Hz), 4.37-4.29 (m, 2H), 1.35 (t, 3H, J = 7.1 Hz). ESLRMS m / z 434 (M + NH 4 + ). FABHRMS m / z 434.0574 (M + NH 4 + , calculated 434.0538). Analytical Calcd C 19 H 13 Cl 2 F 3 O 3 : C, 54.70; H, 3.14; Cl, 17.00. Found: C, 54.79; H, 3. 18; Cl, 16.65. Step 2. Preparation of 6-chloro-8- (4-chlorophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid. The ester of step 1 (0.500 g, 1.20 mmol) was dissolved in a THF: ethanol: water (7: 2: 1, 10 mL) solution, treated with sodium hydroxide (0.48 mL, 1.20 mmol of 2.5N solution) and 18 at room temperature. Stir for hours. The solvent was removed in vacuo and the remainder dissolved in water (10 mL). Diethyl ether (10 mL) was added and the mixture was acidified with concentrated hydrochloric acid. The organic phase was separated and the aqueous phase extracted with diethyl ether (2x10 mL). The combined extracts were dried over MgSO 4 , filtered and evaporated and recrystallized with diethyl ether-hexane to give the title compound as a white solid (0.40 g, 86%): mp 205.5-207.3 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.81 (s, 1H), 7.42 (s, 4H), 7.34 (d, 1H, J = 2.4Hz), 7.25 (s, 1H), 5.69 (q, 1H, J = 6.8 Hz). FABLRMS m / z 387 (MH). ESHRMS m / z 386.9788 (M−H, calculated 386.980259). Analytical Calcd C 17 H 9 Cl 2 F 3 O 3 : C, 52.47; H, 2. 33; Cl, 18.22. Found: C, 52.38; H, 2. 47; Cl, 18.20. Example 126 6-chloro-8- (3-methoxyphenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl-6-chloro-8- (3-methoxyphenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate. In a 100 mL round bottom flask under nitrogen, ethyl-6-chloro-8-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 73, step 2) (1.00 g, 2.31 mmol) and 3-methoxyphenylboronic acid (0.369 g, 2.43 mmol) were dissolved in 1-propanol (50 mL). The mixture was stirred at rt for 0.5 h, allowing the solids to dissolve. The resulting solution was treated with palladium (II) acetate (0.016 g, 0.0693 mmol), triphenylphosphine (0.055 g, 0.208 mmol), sodium carbonate (0.29 g, 2.77 mmol) and deionized water (10 mL). The reaction mixture was heated to reflux for 3 hours. After cooling to rt, the mixture was extracted with ethyl acetate (1 × 150 mL, 2 × 25 mL). The combined organic phases were washed with saturated aqueous NaHCO 3 (50 mL) and brine (2 × 50 mL), dried over MgSO 4 , filtered and concentrated in vacuo to yield a yellow oil. The output was purified by flash chromatography in 0.5% ethyl acetate in hexanes. The solid was recrystallized from hexane to yield the required ester as a white solid (0.60 g, 63%): mp 93.7-95.1 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.69 (s, 1H), 7.35-7.32 (m, 2H), 7.22 (d, 1H, J = 2.6Hz), 7.05-7.03 (m, 2H), 6.96-6.93 ( m, 1H), 5.72 (q, 1H, J = 6.7 Hz), 4.34-4.31 (m, 2H), 1.35 (t, 3H, J = 7.1 Hz). FABLRMS m / z 413 (M + H). ESHRMS m / z 413.0765 (M + H, calculated 413.076747). Analytical Calcd C 20 H 16 ClF 3 O 4 : C, 58.19; H, 3.91; Cl, 8.59. Found: C, 58.33; H, 4. 10; Cl, 8.61. Step 2. Preparation of 6-chloro-8- (3-methoxyphenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid. The ester of step 1 (0.300 g, 0.727 mmol) was dissolved in THF-ethanol-water (7: 2: 1, 10 mL). It was treated with sodium hydroxide (0.29 mL of 2.5N solution, 0.727 mmol) and stirred at rt for 18 h. The solvent was vaporized and the remainder dissolved in water (10 mL). After addition of ether (10 mL), several drops of concentrated hydrochloric acid were dropped. The ether phase was separated and the aqueous phase was extracted with ether (2x10 mL). The combined ether extracts were dried over MgSO 4 , filtered and concentrated in vacuo to recrystallize in diethyl ether-hexane to give the title compound as a white solid (0.23 g, 81%): mp 173.1- 177.4 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.81 (s, 1H), 7.39-7.37 (m, 2H), 7.05-7.04 (m, 2H), 6.97-6.94 (m, 1H), 5.71 (q, 1H, J = 6.7 Hz), 3.85 (s, 3H). ESHRMS m / z 383.0278 (MH, calculated 383.029796). Analytical Calcd C 18 H 12 ClF 3 O 4 : C, 56.20; H, 3. 14; Cl, 9.21. Found: C, 55.90; H, 3.11; Cl, 9.48. Example 127 6-chloro-8-[(4-methylthio) phenyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was prepared in a similar manner to Example 126 above: mp 211.4-212.5 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.94 (s , 1H), 7.57 (d, 1H, J = 2.6Hz), 7.53-7.50 (m, 2H), 7.45 (d, 1H, J = 2.6Hz) , 7.39-7.36 (m, 2H), 5.87 (q, 1H, J = 7.1 Hz), 2.55 (s, 3H). ESHRMS m / z 399.0051 (M−H, calculated 399.0069). Analytical Calcd C 18 H 12 ClF 3 O 3 S: C, 53.94; H, 3.02; C1, 8.84; S, 8.00. Found: C, 53.86; H, 2. 82; C1, 8.91; S, 8.21. Example 128 6-chloro-8-[(4-methylsulfonyl) phenyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl-6-chloro-8-[(4-methyl-sulfonyl) phenyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate. Oxon TM (1.44 g, 2.34 mmol) was dissolved in water (10 mL) and then cooled to 5 ° C. Ethyl-6-chloro-8-[(4-methylthio) phenyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 127, ethyl ester) in methanol (20 mL) (0.5G, 1.17mmol) was added and slowly added to the reaction compound, and the solution was stirred for 5 hours at room temperature. Methanol was then removed in vacuo. The remaining solution was extracted with methylene chloride (2x50 mL). The combined organic phases were dried over MgSO 4 , filtered and distilled to yield a yellow solid. This solid was recrystallized in ether-hexane to give a sulfone which was a white solid (0.46 g, 84%): mp 13.2-146.2 ° C. 1 H NMR (CDCl 3 / 300MHz ) 8.03 (s, 1H), 8.00 (s, 1H), 7.70 (d, 1H, J = 2.4Hz), 7.28 (d, 1H, J = 2.6Hz), 5.71 (q , 1H, J = 6.9 Hz), 4.35-4.32 (m, 2H), 3.11 (s, 3H), 1.35 (t, 3H, J = 7.2 Hz). FABLRMS m / z 467 (M + Li). ESHRMS m / z 478.0707 (M + NH 4 + , calculated 478.070281). Analytical Calcd C 20 H 16 ClF 3 O 5 S: C, 52.12; H, 3.50; Cl, 7.69. Found: C, 52.17; H, 3. 36; Cl, 7.77. Step 2. Preparation of 6-chloro-8-[(4-methylsulphonic) phenyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid. The sulfone of step 1 (0.300 g, 0.651 mmol) was dissolved in a solution of THF: ethanol: water (7: 2: 1; 10 mL). It was treated with sodium hydroxide (0.26 mL, 0.651 mmol of 2.5N solution) and stirred for 18 hours at room temperature. The solvent was removed in vacuo and the remainder was dissolved in water (10 mL). Diethyl ether (10 mL) was added and the mixture was acidified with concentrated hydrochloric acid. The organic phase was separated and the aqueous phase was extracted with diethyl ether (2x10 mL). The combined organic extracts were dried over MgSO 4 , filtered and evaporated to yield a white solid. This solid was recrystallized in ether-hexane to yield the title compound as a white solid (0.20 g, 73%): mp 286.5-287.8 ° C. 1 H NMR (acetone -d 6 / 300MHz) 8.07 (d , 2H, J = 6.7Hz), 7.97 (S, 1h), 7.84 (d, 2H, J = 6.7Hz), 7.67 (d, 1H, J = 2.6 Hz), 7.55 (d, 1H, J = 2.6 Hz), 5.92 (q, 1H, J = 7.1 Hz), 3.20 (s, 1H). ESHRMS m / z 430.9947 (MH, calculated 430.996782). Analytical Calcd C 18 H 12 ClF 3 O 5 S: C, 49.95; H, 2. 80; Cl, 8.19. Found: C, 50.04; H, 2. 80; Cl, 8.25. Example 129 6-chloro-8-phenyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl 6-chloro-8-phenyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate. Ethyl 6-chloro-8-bromo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 74, step 1) (2.0G, 5.2mmol), tetrakis (triphenyl Phosphine) Palladium (O) (2.15 g, 1.7 mmol), triphenyl phosphine (0.013 g, 0.05 mmol) and tributylphenyltin (1.9 mL, 5.7 mmol) were added to toluene (60 mL) for 3 days. Heated to 110 ° C. The reaction mixture was cooled to room temperature and adsorbed with 25% ethyl acetate in hexane and filtered through a silica gel plug. The filtrate was concentrated in vacuo and purified by flash chromatography (silica gel, ethyl acetate-hexane, 1: 9). The portion containing the required product was combined and concentrated in vacuo. To remove remaining tin impurities, the mixture was treated with THF (10 mL) and aqueous ammonium fluoride solution (10 wt%, 20 mL) and stirred at room temperature for 2 hours. The extracts were collected, dried over MgSO 4, filtered and concentrated in vacuo to yield the ester oil (1.30g, 65%): 1 H NMR (CDCl 3 / 300MHz) 7.67 (s, 1H), 7.47-7.36 ( m-5H), 7.31 (d, 1H, J = 2.6 Hz), 7.18 (d, 1H, J = 2.4 Hz), 5.69 (q, 1H, J = 6.8 Hz), 4.30 (m, 2H), 1.33 ( t, 3H, J = 7.1 Hz). 19 FNMR (CDCl 3 / 282MHz) d -78.27 (d, J = 7.2Hz). FABLRMS m / z 383 (M + H). ESHRMS m / z 400.0937 (M + NH 4 , calculated 400.0927). Step 2. Preparation of 6-chloro-8-phenyl-2-trifluoromethyl-2H-1-benzopyran-30carboxylic acid. The ester solution of step 1 (1.0 g, 2.6 mmol) was dissolved in THF (5 mL) and methanol (5 mL) and treated with 2.5N NaOH solution (4.0 mL, 104 mmol). The resulting compound was stirred for 18 hours at room temperature. The solvent was removed in vacuo, the remainder was treated with ethyl acetate and acidified with 3N HCl. The extracts were combined, dried over MgSO 4 , filtered and concentrated in vacuo to yield a yellow solid. Recrystallization from ethyl acetate-hexane gave the title compound as a pale yellow solid (0.42 g, 46%): mp 196.3-197.7 ° C. 1 H NMR (CDCl 3 / 300MHz ) d 7.65 (s, 1H), 7.40-7.23 (m, 6H), 7.15 (s, 1H), 5.63 (q, 1H, J = 6.5Hz), 3.35 (broad s, 1H). 19 F NMR (CDCl 3 / 282MHz ) d -78.71 (d, J = 5.8Hz). FABLRMS m / z 355 (M + H). ESHRMS m / z 353.0198 (M−H, calculated 353.0192). Example 130 6-Bromo-8-fluoro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 4-Bromo-2-fluorophenol was converted to the title compound in a similar procedure as Example 2 above: mp 206-208 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.78 (s, 1 H), 7.36-7.48 (m, 2 H), 5.87 (q, 1 H, J = 6.8 Hz). EIHRMS m / z 339.9349 (calculated 339.9358). Analytical Calcd C 11 H 5 BrF 4 O 3 : C 38.74, H 1.48; Found C 538.97, H, 1.60. Example 131 6- (4-fluorophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-Benzopyran-3-carboxylic acid starts methyl-6-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 24, step 3) Prepared in a similar manner to Example 125 above: mp 207-210 ° C. 1 H NMR (CD 3 OD / 300MHz) 7.87 (s, 1H), 7.54-7.64 (m, 4H), 7.10-7.20 (m, 2H), 7.03 (d, 1H, J = 9.4 Hz), 5.77 (q , 1H, J = 7.0 Hz). EIHRMS m / z 338.0573 (calculated 338.0566) Analytical calculated C 11 H 6 F 3 IO 3 + 1.25% H 2 O: C, 59.62; H, 3.08. Found: C, 59.61; H, 3.09. Example 132 6-phenyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was prepared using starting material of ethyl 6-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 24, step 3). Prepared in a similar manner to Example 125 above: mp 197-198 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.87 (s, 1 H), 7.28-7.64 (m, 7 H), 7.03 (d, 1 H, J = 6.8 Hz), 5.76 (q, 1H, J = 7.0 Hz). EIHRMS m / z 320.0660). Analytical Calcd C 17 H 11 F 3 O 3 : C, 63.75; H 3.46. Found: C, 63.56; H, 3.46. Example 133 8-chloro-6-fluoro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2-Chloro-4-fluorophenyl was converted to the title compound in a similar procedure to Example 2 above: mp 240-241 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.77 (s, 1H), 7.26 (dd, 1H, J = 8.3, 2.9), 7.14 (dd, 1H, J = 8.1, 2.9), 5.87 (q, 1H, J = 6.8 Hz). EIHRMS m / z 295.9836 (calculated 295.9863). Analytical Calcd C 11 H 5 ClF 4 O 3 : C, 44.54; H 1.70. Found: C, 44.70; H, 1.73. Example 134 6,8-Diiodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was prepared in a similar manner to Example 1 above: mp 243-244 ° C. 1 H NMR (CD 3 OD / 300MHz) 8.07 (d, 1H, J = 2.0 Hz), 7.71 (s, 1H), 7.70 (d, 1H, J = 2.0 Hz), 5.89 (q, 1H, J = 6.8 Hz). ESHRMS m / z 494.8174 (calculated MH 494.8202) Analytical calculated C 11 H 5 F 3 I 2 O 3 : C, 26.64; H 1.02. Found: C, 26.75; H, 1.036. Example 135 6- (5-chloro-2-thienyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was used as starting material for ethyl-6-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 72, step 3). Prepared in a similar manner to Example 125 above: mp 205-206 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.83 (s, 1 H), 7.50-7.58 (m, 2 H), 7.14 (d, 1 H, J = 4.0 Hz), 7.00 (d, 1H, J = 8.86 Hz), 6.93 (d, 1H, J = 4.0 Hz), 5.77 (q, 1H, J = 7.0 Hz). EIHRMS m / z 359.9810 (M < + >, calculated 359.9835) Analytical calculated C 15 H 8 ClF 3 O 3 S: C, 49.94; H 2.24. Found: C, 50.14; H, 2.29. Example 136 6- (2-thienyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was prepared using starting material of ethyl 6-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 24, step 3). Prepared in a similar manner to Example 125 above: mp 209-212 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.83 (s, 1H), 7.58-7.62 (m, 2H), 7.30-7.38 (m, 2H), 6.80-7.09 (m, 2H), 5.76 (q, 1H, J = 7.0 Hz) FABHRMS m / z 325.0153 (calculated MH 325.0146). Example 137 6- (4-chlorophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was prepared using starting material of ethyl 6-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 24, step 3). Prepared in a similar manner to Example 125 above: mp 212-213 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.89 (s, 1H), 7.56-7.66 (m, 4H), 7.40-7.48 (m, 2H), 7.04-7.10 (m, 1H), 5.77 (q, 1H, J = 7.0 Hz). ESHRMS m / z 353.0190 (calculated MH 353.0192). Analytical Calcd C 17 H 10 ClF 3 O 3 : C, 57.56; H 2.84. Found: C, 57.41; H, 2.82. Example 138 6- (4-bromophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Start ethyl-6-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate of 2H-1-benzopyran-3-carboxylic acid (Example 24, step 3) The material was prepared in a similar manner to Example 126 above: mp 215-216 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.89 (s, 1 H), 7.06-7.71 (m, 6H), 7.04-7.06 (m, 1H), 5.78 (q, 1H, J = 6.8 Hz). ESHRMS m / z 396.9681 (calculated MH 396.9687). Example 139 6- (ethynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was prepared using starting material of ethyl 6-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 24, step 3). Prepared in a similar manner to Example 118 above: mp 198-200 ° C. 1 H NMR (CD 3 OD / 300MHz) 7.80 (s, 1H), 7.47 (dd, 1H, J = 8.5, 2.0 Hz), 7.41 (d, 1H, J = 2.0 Hz), 6.97 (d, 1H, J = 8.5 Hz), 5.71 (q, 1H, J = 6.8 Hz), 3.06 (s, 1H). ESHRMS m / z 267.0271 (calculated MH 267.0269) Analytical calculated C 13 H 7 F 3 O 3 + 1.06% H 2 O: C, 57.60; H 2.72. Found: C, 57.59; H, 2.62. Example 140 6-methyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 4-methylsalicylaldehyde was converted to a procedure similar to Example 1 above: mp 191.8-193.0 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.80 (s , 1H), 7.72-7.73 (m, 2H), 6.90 (d, 1H, J = 8.4Hz), 5.91 (q, 1H, J = 7.2Hz) . Analytical Calculations C 12 H 9 O 3 F 3 : C, 55.82; H, 3.51. Found: C, 55.89; H, 3.49. Example 141 6-chloro-8- (4-methoxyphenyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid 2H-1-benpyran-3-carboxylic acid was prepared in a similar manner to Example 126 above: mp 194.0-196.0 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.81 (s, 1H), 7.44 (s, 1H), 7.41 (s, 1H), 7.34 (d, 1H, J = 2.4Hz), 7.21 (d, 1H, J = 2.4 Hz), 6.99 (s, 1 H), 6.96 (s, 1 H), 5.69 (q, 1 H, J = 6.7 Hz), 3.86 (s, 3H). FABLRMS m / z 402.2 (M + NH 4 ). ESHRMS m / z 383.0267 (M−H, calcd 383.029796). Analytical Calcd C 18 H 12 ClF 3 O 4 : C, 56.20; H, 3. 14; Cl, 9.21. Found: C, 56.08; H, 3.11; Cl, 9.13. Example 142 6-chloro-2- (trifluoromethyl) -4-ethenyl-2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl 3- (5-chloro-2-hydrophenyl) -3-oxo-propionate. Lithium hexamethyldisilazide solution (800 mL of 1 M solution of THF, 800.0 mmol) was cooled to -78 ° C in a nitrogen atmosphere. A 5-chloro-2-hydroxyacetophenone (45.493 g, 266.67 mmol) solution was added dropwise to THF (130 mL) and stirred for 0.5 h. The reaction proceeded at −78 ° C. for 1 hour, warmed at −10 ° C. for two hours, warmed to 0 ° C. for 1 hour, and then cooled to −78 ° C. again. Diethyl carbonate (35.54 mL, 34.65 g, 29.34 mmol) was added little by little with an injector. The temperature was maintained at −78 ° C. for 0.5 h and stirred for 3 h. The reaction mixture was carefully added to a mixture of rapidly stirred ice (1200 mL) / conc HCl (222 mL). The phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with brine, dried over Na 2 SO 4 , filtered in vacuo and concentrated to yield an oil which started to crystallize. The crystal product was obtained by vacuum filtration and the title compound (29.04 g, 45%) yielded as brown needle-shaped crystals: mp 71.8-73.1 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.63 (d, 1H, J = 2.4Hz), 7.45 (dd, 1H, J = 8.9, 2.6), 6.98 (d, 1H, J = 8.9Hz), 4.25 (q, 2H, J = 7.3 Hz), 3.98 (s, 2H), 1.29 (t, 3H, 7.3 Hz). FABLRMS m / z 249 (M + Li). EIHRMS m / z 242.0346 (M < + >, calculated 242.0346). Analytical Calcd C 11 H 11 ClO 4 : C, 54.45; H, 4.57. Found: C, 54.48; H, 4.62. Step 2. Preparation of ethyl-2- (trifluoromethyl) -6-chloro-4-oxo-4H-1-bonzepyran-3-carboxylate. Keto-ester (step 1) (19.2 g, 79.1 mmol) was added to trifluoroacetic anhydride (67.2 mL, 49.9 g, 475.8 mmol), potassium carbonate (44 g, 318 mmol) and toluene (400 mL). This suspension was stirred at rt for 36 h and heated to reflux for 4 h. After cooling to room temperature, the suspension was added to rapidly stirred (mechanical stirrer) ice (300 mL) and aqueous HCl solution (12N, 50 mL). The resulting organic phase was separated from the clear mixture, washed with water (5 × 500 mL), brine (1 × 500 mL), dried over MgSO 4 , filtered in vacuo and concentrated to yield a dry brown solid under high vacuum. This sample was partially dissolved in heptane (100 mL) and ethyl acetate (12 mL) in a steam electrolyzer and filtered to remove insoluble matter. The filtrate was cooled to room temperature to yield the required 4-oxo-4H-1-benzopyran, a fluffy brown solid (14.17 g, 56%): mp 106.7-108.6 ° C. This material was pure enough for use in the next step without further purification. Step 3. Preparation of ethyl 2- (trifluoromethyl) -4-oxo-dihydro-1-benzopyran-3-carboxylate. A stirred and cooled (0 ° C.) ketone (step 2) (6.92 g, 21.58 mmol) solution was added to THF (40 mL) and ethanol (50 mL) and treated with NaBH 4 (0.41 g, 10.79 mmol). After 3 hours additional NaBH 4 (0.30 g, 7.93 mmol) was added in portions over 1 hour. The reaction was added to a rapidly stirred cold aqueous HCl solution (15 mL of 12N HCl diluted to 300 mL). During the addition a precipitate was produced which was filtered off by vacuum filtration and dried under high vacuum to yield the required substituted 4-oxo-dihydro-1-benzopyran as a white powder (6.92 g, 99%): mp 80.2-84.9 ° C. 1 H NMR (CDCl 3 / 300MHz ) 12.60 (br s, 1H), 7.69 (d, 1H, J = 2.6Hz), 7.34 (dd, 1H, J = 2.6, 8.7Hz), 6.93 (d, 1H, J = 8.7 Hz), 5.59 (q, 1H, J = 6.6 Hz), 4.46-4.23 (m, 2H), 1.35 (t, 3H, 7.0 Hz). FABLRMS m / z 329 (M + Li). EIHRMS m / z 322.0213 (M < + >, 322.0220). Analytical calculation Cl 3 H 10 Cl 1 F 3 O 4 3.57% H 2 O: C, 46.67; H, 3.41. Found: C, 46.62; H, 3.14. Step 4. Preparation of ethyl-6-chloro-4- (trifluoromethanesulfonoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate. A 50 mL molton flask was equipped with septa and funnel, 2,6-di-tert-butylpyridine (1.782 g, 8.679 mmol), methylene chloride (15 mL) and trifluoromethanesulfonine anhydride (1.22 mL, 2.04 g, 7.23 mmol) Was added and chromman-4-one (step 3) (2.145 g, 5.786 mmol) in methylene chloride (12 mL) was added dropwise over 0.33 h. After stirring for 16 hours at room temperature, the reaction was concentrated in vacuo and diluted with diethyl ether (50 mL) to yield a suspension. The suspension is vacuum filtered, the filtrate is washed with cold 2N HCl and brine, dried over MgSO 4 , filtered and concentrated in vacuo to give the desired tree a pale yellow powder (1.45 g, 55%) suitable for use without further purification. Plates were calculated: mp 51.9-53.2 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.46 (d, 1H, J = 2.4Hz), 7.28-7.14 (m, 2H), 6.96 (d, 1H, J = 8.7Hz), 5.77-5.71 (m, 2H) , 5.38 (dd, J = 1.2, 17.9 Hz), 4.32-4.26 (m, 2H), 1.33 (t, 2H, J = 7.1 Hz). FABLRMS m / z 333.2 (M + H). ESHRMS m / z 333.0510 (M + H, calculated 333.050532). Analytical Calculations C 15 H 12 ClF 3 O 3 (1.14 wt% H 2 O): C, 53.53; H, 3. 72; Cl, 10.53. Found: C, 53.46; H, 3. 42; Cl, 10.70. Step 6. Preparation of 6-chloro-4-ethenyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid. The ester of step 5 (0.300 g, 0.902 mmol) was dissolved in THF-EtOH-H 2 O mixture (10 mL, 7: 2: 1) and treated with sodium hydroxide (0.360 mL, 0.902 mmol of 2.5N solution). This solution was stirred for 18 hours at room temperature. Diethyl ether (10 mL) was added and the mixture was acidified by addition of concentrated HCl. The organic phase was separated and the aqueous phase was extracted with diethyl ether (2x10 mL). The ether extracts were combined, dried over MgSO 4 , filtered and concentrated in vacuo to yield a yellow solid which was recrystallized from diethyl ether-hexane to yield the title compound as a white solid (0.163 g, 59%): mp 143.0-145.0 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.49 (d, 1H, J = 2.6Hz), 7.33-7.17 (m, 2H), 6.99 (d, 1H, J = 8.5Hz), 5.82-5.72 (m, 2H) , 5.42 (d, 1H, J = 17.9 Hz). ESHRMS m / z 303.00207 (MH, calculated 303.003582). Analytical Calcd C 13 H 8 ClF 3 O 3 (1.10 wt% H 2 O): C, 50.69; H, 2. 74; Cl, 11.51. Found: C, 50.57; H, 2. 37; Cl, 11.75. Example 143 6-chloro-2- (trifluoromethyl) -4-phenyl-2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was added to ethyl-6-chloro-4- (trifluoromethanesulfonoxy) -2- (tri in a similar manner to that described in Example 142, steps 5-6. Fluoromethyl) -2H-1-benzopyran-3-carboxylate (Example 142, step 4): mp 225.5-226.6 ° C. 1 H NMR (DMSO- d6 / 300 MHz). 7.46-7.39 (m, 4H), 7.20-7.13 (m, 3H), 6.52 (d, 1H, J = 2.42 Hz), 6.12 (q, 1H, J = 7.1 Hz). FABLRMS m / z 355.1 (M + H). ESHRMS m / z 353.0215 (M−H, calculated 353.019232). Analytical Calcd C 17 H 10 ClF 3 O 3 : C. 57.56; H, 2. 84; Cl, 10.17. Found: C, 57.18; H, 2. 66; Cl, 10.17. Example 144 6-chloro-4- (2-thienyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 2H-1-benzopyran-3-carboxylic acid was prepared in a procedure similar to that described in Example 142, Steps 5-6, ethyl 6-chloro-4- (trifluoromethanesufonoxy) -2- (trifluoro Methyl) -2H-1-benzopyran-3-carboxylate (Example 142, step 4): mp 200.8-206.7 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.52 (dd, 1H, J = 1.21, 5.04Hz), 7.28 (dd, 1H, J = 2.42, 8.67Hz), 7.15 (dd, 1H, J = 1.21, 3.42Hz) , 6.98-6.93 (m, 2H), 5.83 (q, 1H, J = 6.9 Hz). FABLRMS m / z 378 (M + NH 4 ). Analytical Calcd C 15 H 8 ClF 3 O 3 S: C, 49.94; H, 2. 24; C1, 9.83; S, 8.89. Found: C, 50.02; H, 1.98; C1, 9.34; S. 8.89. Example 145 6-Methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid Step 1. Preparation of 5-methyl-2-mercaptobenzaldehyde. Tetramethylethylenediamine (TMEDA) (12.6 mL, 83.5 mmol) was added to n-BuLi (33 mL of 1.6 M in hexane, 82.5 mmol) with an injector, and the solution was cooled to 0 ° C. A solution of p-thiocresol (4.53 g, 36.5 mmol) in cyclohexane (40 mL) was stirred for 5 minutes. The resulting brown slurry was stirred for 1.3 h at room temperature. The reaction mixture was added to 3N HCl (150 mL). This mixture was extracted with ethyl acetate. The combined organics were washed with brine, dried over MgSO 4 , filtered and concentrated in vacuo to give a brown oil. This oil was purified by flash chromatography on silica gel by adsorbing 10% ethyl acetate-hexane and yielding 5-methyl-2-mercaptobenzaldehyde (4.47 g, 69%) as an appropriate dark yellow solid without further purification. Step 2. Preparation of ethyl-6-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylate. 5-Methyl-2-mercaptobenzaldehyde (step 1) (3.25 g, 21.3 mmol) was added to DMF (5 mL) and ethyl 4,4,4-trifluorocrotonate (4.32 g, 25.7 mmol). Occlusion was added to K 2 CO 3 (3.78 g, 27.3 mmol) to make the reaction dark red. The reaction was stirred at rt for 20 h, acidified with 3N HCl, diluted with ethyl acetate, washed with water, saturated NaHCO 3 solution, brine, dried over MgSO 4 , filtered in vacuo and concentrated to yield an oil. It was. The oil was crystallized with diethyl ether-petroleum ether to give ethyl-6-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylate as a pale yellow solid (4.47 g, 69%). Calculated: mp 93.1-94.7 ° C. 1 H NMR (acetone-d6 / 300 MHz) 7.94 (s, 1 H), 7.41 (s, 1 H), 7.31 (d, 1 H, J = 7.9 Hz), 7.25 (d, 1H, J = 7.9 Hz), 4.96 ( q, 1H, J = 8.5 Hz, 4.33 (m, 2H), 2.34 (s, 3H), 1.35 (t, 3H, J = 7.0 Hz). FABLRMS m / z 309 (M + Li). Step 3. Preparation of 6-Methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid. The ester of step 2 (0.55 g, 1.8 mmol) was dissolved in THF (1.5 mL) and ethanol (1.5 mL), treated with 2.5N sodium hydroxide (1.5 mL, 3.8 mmol) and stirred at room temperature for 88 hours. The reaction compound was concentrated in vacuo, acidified with 3N HCl, filtered and recrystallized from diethyl ether / petroleum ether to yield the title compound as a yellow solid (0.14 g, 28%): mp 180.8-184.2 ° C .. 1 H NMR (acetone-d6 / 300 MHz) 7.95 (s, 1 H), 7.42 (s, 1 H), 7.31 (d, 1 H, J = 8.1 Hz), 7.25 (d, 1H, J = 8.1 Hz), 4.94 ( q, 1H, J = 8.7 Hz), 2.34 (s, 3H). FABLRMS m / z 281 (M + Li). EIHRMS m / z 274.0250 (M < + >, 274.0275). Analytical Calcd C 12 H 9 F 3 O 2 S: C, 52.55; H, 3.31. Found: C, 52.54; H, 3.35. Example 146 6,8-dimethyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid 2H-1-benzothiopyran-3-carboxylic acid was prepared in a similar manner to Example 145 above: mp 220-225 ° C.) (dec). 1 H NMR (acetone-d6 / 300 MHz) 11.5 (brs, 1H), 7.94 (s, 1H), 7.26 (s, 1H) 7.14 (s, 1H), 4.98 (q, 1H, J = 8.7 Hz), 2.34 (s, 3 H), 2.31 (s, 3 H). FABLRMS m / z 295 (M + Li). EIHRMS m / z 288.0431 (M < + >, 288.0432). Analytical calculation C 13 H 11 F 3 O 2 S: C, 54.16; H, 3.85. Found: C, 54.10; H, 3.91. Example 147 6- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid 2H-1-benzothiopyran-3-carboxylic acid was prepared by a similar procedure as in Example 145 above: mp 183.8-184.6 ° C. 1 H NMR (acetone-d6 / 300 MHz) 8.04 (s, 1H), 7.68 (d, 1H, J = 2.2 Hz), 7.46 (d, 1H, J = 8.3 Hz 2.2 Hz), 7.37 (d, 1H, J = 8.3 Hz), 4.94 (q, 1H, J = 8.7 Hz), 1.34 (s, 9H). FABLRMS m / z 334 (M + NH 4 ). ESHRMS m / z 334.1087 300 MHz) 7.52 (dd, 1H, J = 1.21, 5.04 Hz), 7.28 (dd, 1H, J = 2.42, 8.67 Hz), 7.15 (dd, 1H, J = 1.21, 3.42 Hz), 6.98 -6.93 (m, 2H), 5.83 (q, 1H, J = 6.9 Hz). FABLRMS m / z 378 (M + NH 4 ). Analytical Calcd C 15 H 8 ClF 3 O 3 S: C, 49.94; H, 2. 24; C1, 9.83; S, 8.89. Found: C, 50.02; H, 1.98; C1, 9.34; S, 8.89. (M + NH 4 , calc. 334.1089). Analytical Calcd C 15 H 15 F 3 O 2 S: C, 56.95; H, 4.78. Found: C, 57.03; H, 4.83. Example 148 7-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid A procedure similar to the method described in Example 145 above was prepared with 2H-1-benzothiopyran-3-carboxylic acid: mp 186.6-191.9 ° C. 1 H NMR (acetone-d6 / 300 MHz) 7.96 (s, 1 H), 7.49 (dd, 1 H, J = 7.6 Hz 2.82 Hz), 7.27 (s, 1H), 7.14 (d, 1H, J = 7.6 Hz), 4.96 (q, 1H, J = 5.3 Hz), 2.36 (s, 3H). ESHRMS m / z 273.0204 (MH, calculated 273.0197). Analytical Calcd C 12 H 9 F 3 O 2 S (3.32 wt% H 2 O): C, 50.81; H, 3.57. Found: C, 50.79; H, 3.44. Example 149 6,7-dimethyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid 2H-1-benzothiopyran-3-carboxylic acid was prepared in a similar manner to the method described in Example 145 above: mp 235-237 ° C. 1 H NMR (acetone-d6 / 300 MHz) 7.90 (s, 1 H), 7.33 (s, 1 H), 7.19 (s, 1 H), 4.91 (q, 1 H, J = 8.7 z), 2.28 (s, 3 H), 2.26 (s, 3 H). FABLRMS m / z 295 (M + Li). EIHRMS m / z 288.0439 (M < + >, 288.0432). Analytical calculation C 13 H 11 F 3 O 2 S: C, 54.16; H, 3.85. Found: C, 54.13; H, 3.85. Example 150 8-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid 2H-1-benzothiopyran-3-carboxylic acid was prepared in a similar manner to the method described in Example 145 above: mp 224-225 ° C. 1 H NMR (acetone-d6 / 300 MHz) 11.60 (br s, 1H), 8.00 (s, 1H), 7.44 (d, 1H, J = 6.7 Hz), 7.31 (d, 1H, J = 6.8 Hz), 7.21 (m, 1H), 5.05 (q, 1H, J = 8.5z), 2.38 (s, 3H), 2.26 (s, 3H). FABLRMS m / z 292 (M + NH 4 ). ESHRMS m / z 292.0591 (M + NH 4 , calculated 292.0619). Analytical Calcd C 12 H 9 F 3 O 2 S: C, 52.55; H, 3.31. Found: C, 52.62; H, 3.38. Example 151 2- (Trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid 2H-1-benzothiopyran-3-carboxylic acid was prepared in a similar manner to the method described in Example 145 above: mp 187-190 ° C. 1 H NMR (acetone-d6 / 300 MHz) 8.01 (s, 1H), 7.60 (d, 1H, J = 7.5 Hz), 7.45 (m, 2H), 7.31 (m, 1H), 4.98 (q, 1H, J = 8.7z). ESHRMS m / z 259.0070 (M−H, calculated 259.0041). Analytical Calcd C 11 H 7 F 3 O 2 S: C, 50.77; H, 2.71. Found: C, 50.75; H, 2.78. Example 152 6-chloro-7-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid Step 1. Preparation of N, N-dimethyl-O- (4-chloro-2-formyl-5-methylphenyl) thiocarbamate. A mixture of 5-chloro-4-methylsalicylaldehyde (12.96 g, 76.0 mmol) and triethylamine (11.58 g, 114.4 mmol) was treated with N, N-dimethylthiocarbamoyl chloride (11.25 g, 91.0 mmol). It was dissolved in anhydrous DMF (15 mL) and stirred at rt for 16 h. The reaction was treated with 3N HCl (50 mL) and filtered to yield an orange solid. The solid was dissolved in ethyl acetate, washed with 3N HCl, water, brine, dried over anhydrous MgSO 4 , filtered and concentrated in vacuo to give a brown solid (16.79 g) which was recrystallized from diethyl ether / hexane to give a brown solid O-aryl thiocarbamate, (4.92 g, 25%), was calculated: 1 H NMR (acetone-d6 / 300 MHz) 9.96 (s, 1H), 7.80 (s, 1H), 7.19 (s, 1H), 3.46 (s, 3H), 3.42 (s, 3H), 2.43 (s, 3H). Step 2. Preparation of N, N-dimethyl-S- (4-chloro-2-formyl-5-methylphenyl) thiocarbamate. O-aryl thiocarbamate (step 1) (4.92 g, 19.1 mmol) was dissolved in N, N-dimethyl aniline (25 mL) and soaked and stirred at 200 ° C. for 1.5 h. The reaction mixture was cooled to room temperature and added to a mixture of 3N HCl (200 mL) and ice. Filtration gave a brown semisolid, which was dissolved in ethyl acetate, washed with 3N HCl brine, dried over anhydrous MgSO 4 , filtered and concentrated in vacuo to be used as a brown oil (3.80 g, 77%) for the next step without further purification. Arylthiocarbamate was calculated. Step 3. Preparation of ethyl-6-chloro-7-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylate. S-aryl thiocarbamate (step 2) (3.80 g, 14.7 mmol) was dissolved in THF (10 mL) and ethanol (10 mL), treated with 2.5N sodium hydroxide (16.5 mL, 34.2 mmol) and stirred at room temperature for 0.9 h. It was. The reaction was diluted in diethyl ether, washed with 3N HCl, brine, dried over MgSO 4 , filtered in vacuo and concentrated to yield substituted 2-mercaptobenzaldehyde as a brown solid (2.82 g). The oil was added to DMF (10 mL) and ethyl 4,4,4-trifluorocrotonate (3.89 g, 23.1 mmol). Stirring was added to 3.23 g, 23.4 mmol) of K 2 CO 3 so that the reaction was concentrated. The reaction was stirred at rt for 14.5 h, acidified with 3N HCl and extracted with ethyl acetate. The resulting organic phase was washed with brine, dried over MgSO 4 , filtered in vacuo and concentrated to yield a yellow solid (6.36 g) to be used in the next step without further purification. Step 4. Preparation of 6-chloro-7-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid. The ester of step 3 (2.02 g, 6.0 mmol) was dissolved in THF (10 mL) and ethanol (10 mL), treated with 2.5N sodium hydroxide (5.5 mL, 13.8 mmol) and stirred at room temperature for 4.8 h. The reaction compound was concentrated in vacuo and acidified with 3N HCl to yield a suspension. Filtration gave a solid which was then recrystallized from ethanol-water to yield the title compound as a yellow solid (0.20 g, 11%): mp 240.5-241.7 ° C. 1 H NMR (acetone-d6 / 300 MHz) 7.99 (s, 1 H), 7.67 (s, 1 H), 7.43 (s, 1 H), 4.99 (q, 1 H, J = 8.5 Hz), 2.39 (s, 3H). FABLRMS m / z 307 (M−H). FABHRMS m / z 306.9831 (M−H, calcd 306.9807). Analytical Calcd C 12 H 8 ClF 3 O 2 S: C, 46.69; H, 2.61; Cl, 11.48. Found: C, 46.78; H, 2.61; Cl. 11.41. Example 153 7-chloro-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid A procedure similar to the method described in Example 152 above was prepared with 2H-1-benzothiopyran-3-carboxylic acid: mp 225.7-227.3 ° C. 1 H NMR (acetone-d6 / 300 MHz) 8.02 (s, 1H), 7.63 (d, 1H, J = 8.3 Hz), 7.54 (d, 1H, J = 2.0 Hz), 7.36 (d, 1H, J = 8.3 Hz 2.0 Hz), 5.04 (q, 1H, J = 8.5 Hz). ESHRMS m / z 292.9646 (M−H, calculated 292.9651). Example 154 6,7-dichloro-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid 2H-1-benzothiopyran-3-carboxylic acid was prepared in a similar manner to the method described in Example 152 above: mp 262.5-263.5 ° C. 1 H NMR (acetone-d6 / 300 MHz) 8.04 (s, 1 H), 7.90 (s, 1 H), 7.74 (s, 1 H), 5.09 (q, 1 H, J = 8.5 Hz). ESHRMS m / z 326.9242 (M−H, calcd 326.9261). Example 155 2- (Trifluoromethyl) -6-[(trifluoromethyl) thio] -2H-1-benzothiopyran-3-carboxylic acid 2H-1-benzothiopyran-3-carboxylic acid was prepared in a similar manner to the method described in Example 152 above: mp 129.3-132.4 ° C. 1 H NMR (acetone-d6 / 300 MHz) 8.10 (s, 2H), 8.00 (s, 2H), 7.71 (d, 2H, J = 8.1 Hz), 7.65 (d, 2H, J = 8.1 Hz), 5.09 ( q, 1H, J = 8.5 Hz). ESHRMS m / z 358.9630 (M−H, calculated 358.9635). Example 156 6,8-dichloro-2-trifluoromethyl-2H-1-benzothiopyran-3-carboxylic acid 2H-1-benzothiopyran-3-carboxylic acid was prepared in a similar manner to the method described in Example 152 above: mp 217.9-220.3 ° C. 1 H NMR (acetone-d6 / 300 MHz) 12.50-11.20 (br s, 1H exch.), 8.06 (s, 1H), 7.75 (d, 1H, J = 2.0 Hz), 7.64 (d, 1H, J = 2.2 Hz), 5.23 (q, 1H, J = 8.5 Hz). ESLRMS m / z 327 (MH). ESHRMS m / z 326.9272 (M−H, calcd 326.9261). Example 157 6-chloro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid Step 1. Preparation of 2-amino-5-chlorobenzaldehyde. 2-amino-5-chlorobenzyl alcohol (4.8 g, 30 mmol) and active manganese oxide (IV) (21 g, 240 mmol) were refluxed in chloroform (100 mL) for 1 hour. The reaction was cooled, filtered through diatomaceous earth and concentrated in vacuo yielding 2-amino-5-chlorobenzaldehyde as a dark solid (4.14 g, 81%): mp 74-76 ° C. 1 H NMR (CDCl 3 / 300MHz ) 9.80 (s, 1H), 7.42 (s, 1H), 7.23 (d, 1H, J = 7.0Hz), 6.60 (d, 1H, J = 7.0Hz). Step 2. Preparation of ethyl-6-chloro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylate. 2-amino-5-chlorobenzaldehyde (15.0 g, 96 mmol), anhydrous potassium carbonate, ethyl 4,4,4-trifluorocarbonate (34 mL, 200 mmol) of step 1 was mixed with anhydrous dimethylformamide (60 mL) 7 Heat at 100 ° C. for hours. The reaction was cooled and separated into ethyl acetate (200 mL) and water (200 mL). The aqueous phase was extracted with ethyl acetate (1 × 100 mL). The ethyl acetate extracts were combined and washed with brine (1 × 200 mL), dried over MgSO 4 and concentrated in vacuo to yield a solidified dark oil. The solid was purified by flash chromatography (silica gel: ethyl acetate-sec acid, 1: 9). The portion containing the required product is collected, concentrated in vacuo and the remainder recrystallized from ethyl acetate-hexane to give the yellow high-line ethyl 6-chloro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylate (16.36 g, 56%) was calculated: mp 132.6-134.2 ° C. 1 H NMR (CDCl 3 , 300 MHz) 7.61 (s, 1H), 7.10 (m, 2H), 6.55 (d, 1H, J = 8.0 Hz), 5.10 (q, 1H, J = 6.0 Hz), 4.55 (brs , 1H), 4.23 (m, 2H), 1.32 (t, 3H, J = 7.0 Hz). FABHRMS m / z 306.0468 (M + H + , calculated 306.0509). Analytical Calcd C 13 H 11 NO 2 F 3 Cl: C, 51.08; H, 3.63; N, 4.58. Found: C, 50.81; H, 3. 49; N, 4.72. Step 3. Preparation of 6-Chloro-1,2-dihydro-2- (trifluoro-methyl) -3-quinolinecarboxylic acid. The ester of step 2 (1.7 g, 5.6 mmol) and 2.5N sodium hydroxide (4.4 mL, 11 mmol) were mixed in THF (25 mL), methanol (10 mL) and water (25 mL). After stirring overnight, the reaction was concentrated in vacuo to remove THF and methanol. The remaining aqueous solution was extracted with diethyl ether (2x100 mL). The resulting aqueous phase was acidified with 2N HCl to form an oil precipitate. The oil was adsorbed with ethyl acetate-hexane (1: 1) and purified by flash chromatography on silica gel. The portion containing the required product was collected and concentrated in vacuo. The remainder was triturated with dichloromethane and filtered to afford the yellow solid 6-chloro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarbholic acid (0.645 g, 41%): mp 187.8 -188.8 ° C. 1 H NMR (acetone-d 6 , 300 MHz) 7.69 (s, 1 H), 7.36 (s, 1 H), 7.15 (d, 1 H, J = 8.0 Hz), 6.83 (d, 1H, J = 8.0 Hz), 6.60 (brs, 1 H), 5.20 (m, 1 H), ESHRMS m / z 276.0040 (M−H, calc. 276.0039). Analytical Calcd C 11 H 7 NO 2 F 3 Cl + 2.6% H 2 O: C, 46.39; H, 2.98; N, 4.92. Found: C, 45.99; H, 2.54; N, 4.85. Example 158 6-8-dicolol-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid 1,2-Dihydro-3-quinolinecarboxylic acid was prepared by a procedure similar to that described in Example 157 above: mp 223.4-225.7 ° C. 1 H NMR (acetone-d 6 , 300 MHz) 7.82 (s, 1 H), 7.40 (m, 2 H), 6.53 (brs, 1 H), 5.40 (m, 1 H). ESHRMS m / z 309.9657 (MH, calculated 309.9649). Analytical Calcd C 11 H 6 NO 2 F 3 Cl 2 : C, 42.34; H, 1.94; N, 4.49. Found: C, 42.20; H, 1. 74; N, 4.52. Example 159 6,7-difluoro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid 1,2-dihydro-3-quinolinecarboxylic acid was prepared by a procedure similar to that described in Example 157 above: mp 186.6-188.9 ° C. 1 H NMR (acetone-d 6 , 300 MHz) 7.79 (s, 1 H), 7.32 (m, 1 H), 6.71 (m, 1 H), 6.64 (brs, 1 H), 5.21 (m, 1 H). ESHRMS m / z 278.0262 (M−H, calculated 278.0240). Analytical calculation C 11 H 6 NO 2 F 5 + 1.58% H 2 O: C, 46.58; H, 2. 31; N, 4.94. Found: C, 46.20; H, 2.07; N, 4.54. Example 160 6-iodo-1,2-dipidro-2- (trifluoromethyl) -3-quinolinecarboxylic acid Step 1. Preparation of ethyl 6-iodo-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylate. 5-iodo-2-aminobenzaldehyde (24.0 g, 96.7 mmol), diazbicyclo [2,2,2] -undec-7-ene (32.2 g, 212.0 mmol) and ethyl 4,4,4-tri Fluorocrotonate (35.7 g, 212.0 mmol) was heated to 60 ° C. for 1 h in 1,3-dimethyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidinone (48 mL). The solution was cooled to room temperature and the solution was added to ethyl acetate-hexane (1: 1, 500 mL). The solution was extracted with 2.5N aqueous hydrochloric acid solution (2 × 20 mL) and saturated with aqueous ammonium chloride (2 × 200 mL), dried over sodium sulfide, filtered in vacuo and concentrated. The resulting dark yellow oil was dissolved in hexane (100 mL) to form fine yellow crystals. The suspension was vacuum filtered to yield ethyl 6-iodo-1,2-dihydro-2- (trifluoromethyl) -30quinolinecarboxylate (19.3 g, 50% yield) as fine yellow crystals: mp 137- 138 ° C. 1 H NMR (CDCl 3 , 300 MHz) 7.62 (s, 1H), 7.36-7.48 (m, 2H), 6.43 (d, J = 8.2 Hz), 5.36 (brs, 1H), 5.11 (q, 1H, J = 7.1 Hz), 4.25-4.35 (m, 2H), 1.34 (t, 3H, J = 7.0 Hz). ESHRMS m / z 395.9716 (M−H, calculated 395.9708). Step 2. Preparation of 6-iodo-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid. Hydrolysis of the ester (step 1) was carried out in a procedure similar to that described in Example 157 above to yield a carboxylic acid: mp 188-192 ° C. 1 H NMR (CD 3 OD, 300 MHz) 7.668 (s, 1H), 7.46 (d, 1H, J = 2.2 Hz), 7.39 (dd, 1H, J = 8.4, 2.2 Hz), 6.52 (d, 1H, J = 8.4 Hz), 5.01 (q, 1H, J = 7.5 Hz). ESHRMS m / z 367.9401 (M−H, calculated 367.9395). Example 161 6-bromo-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid. 1,2-dihydro-3-quinolinecarboxylic acid was prepared by a procedure similar to that described in Example 160 above: mp 185-186 ° C. 1 H NMR (CDCl 3 , 300 MHz) 7.68 (s, 1 H), 7.31 (d, 1 H, J = 2.2 Hz), 7.23 (dd, 1 H, J = 8.7, 2.2 Hz), 6.64 (d, 1H, J = 8.7 Hz), 5.01 (q, 1H, J = 7.5 Hz). EIHRMS m / z 319.9519 (M, calculated 319.9534). Analytical Calcd C 11 H 7 BrF 3 NO 2 : C, 41.02; H, 2. 19; N, 4.35. Found: C, 41.27; H, 2. 23; N, 4.26. Example 162 1,2-dihydro-6- (trifluoromethoxy) -2- (trifluoromethyl) -3-quinolinecarboxylic acid Step 1. Preparation of 2-amino-5- (trifluoromethoxy) benzoic acid. 5- (trifluoromethoxy) satin (15.0 g, 65 mmol) and potassium hydroxide tablets (4 g) were mixed in water (35 mL) and cooled to 0 ° C. Under vigorous stirring, a solution of 30% aqueous hydrogen peroxide (11.7 g), purified potassium hydroxide (5.8 g) and water (80 mL) was added dropwise while maintaining the temperature below 10 ° C. After stirring at 0 ° C. for 1 hour, acetic acid (22 mL) of ice crystals was added portionwise to form bubbles and precipitates. The reaction was stirred overnight and filtered to form 2-amino-5-trifluoromethoxy benzoic acid (12.5 g, 87%) as a tan solid. A small amount was obtained by recrystallization from ethyl acetate-hexane, yielding the needle-shaped analytical sample and the compound to be used without further purification: mp 142.5-144.2 ° C. 1 H NMR (CDCl 3 , 300 MHz) 7.98 (s, 1 H), 7.18 (d, 1 H, J = 8.0 Hz), 6.62 (d, 1H, J = 8.0 Hz), 6.40 (brs, 2H). Analytical calculation C 8 H 6 NO 3 F 3 : C, 43.45; H, 2.73; N, 6.33. Found: C, 43.40; H, 2. 65; N, 6.35. Step 2. Preparation of 2-amino-5- (trifluoromethoxy) benzyl alcohol. 2-amino-5-trifluoromethoxybenzoic acid (2.0 g, 9.0 mmol) was added to THF (20 mL) and borane methyl sulfide complex (1.5 mL, 15.0 mmol) mixed with THF (5 mL) was added dropwise. The reaction was refluxed overnight and cooled. A solution of 30% aqueous hydrogen peroxide (0.5 mL), 2.5N sodium hydroxide (0.5 mL) and water (10 mL) was mixed and stirred for 0.5 h. After diluting diethyl ether (50 mL), the organic phase was washed with 0.1 M aqueous sodium meta-bisulfite (2 × 10 mL). The organic phase was further diluted with hexane (50 mL), washed with brine (2x20 mL), dried over anhydrous Na 2 SO 4 , and concentrated in vacuo to yield a solid tan oil (1.9 g). The solid was recrystallized from ethyl acetate-hexane to give 2-amino-5-trifluoromethoxybenzyl alcohol (1.44 g, 77%) as a light tan solid: mp 75.9-77.6 ° C. 1 H NMR (CDCl 3 , 300 MHz) 7.00 (m, 2H), 6.65 (d, 1H, J = 8.0 Hz), 4.05 (s, 2H), 3.25 (brs, 3H). ESHRMS m / z 208.0592 (M + H + , calculated 208.0585). Analytical Calcd C 8 H 8 NO 2 F 3 : C, 46.39; H, 3.89; N, 6.76. Found: C, 46.61; H, 3.79; N, 6.71. Step 3. Preparation of 2-amino-5- (trifluoromethoxy) -benzaldehyde. 2-amino-5-trifluoromethoxybenzyl alcohol (9.7 g, 47 mmol) and manganese oxide (IV) (21 g, 240 mmol) in step 2 were refluxed in chloroform (200 mL) for 1 hour. The reaction was cooled and filtered. The filtrate was concentrated in vacuo to yield a solid tan oil (8.2 g). The oil was distilled at 50 ° C. (0.1 mmol) (bulb to bulb) to yield a yellow solid (7.2 g). The solid was recrystallized from hexane to give the required 2-amino-5- (trifluoromethoxy) -benzaldehyde (4.4 g, 46%) as yellow crystals: mp 42-44 ° C. 1 H NMR (CDCl 3 , 300 MHz) 9.81 (s, 1 H), 7.36 (s, 1 H), 7.20 (d, 1 H, J = 9.0 Hz), 6.64 (d, 1H, J = 9.0 Hz). EIHRMS m / z 205.0328 (M + , calculated 205.0350). Step 4. Preparation of ethyl 1,2-dihydro-6- (trifluoro-methoxy) -2- (trifluoromethyl) -3-quinolinecarboxylate. 2-amino-5- (trifluoromethoxy) benzaldehyde (5.3 g, 26 mmol), anhydrous potassium carbonate (6.9 g, 50 mmol) and ethyl 4,4,4-trifluoro crotonate (7.7 mL, 50 mmol) in step 3 ) Was mixed in anhydrous dimethylformamide (50 mL) and heated to 90 ° C. for 6 h. The reaction was cooled to room temperature and separated between ethyl acetate (200 mL) and water (200 mL). The aqueous phase was extracted with additional ethyl acetate (100 mL). The ethyl acetate extracts were combined, washed with brine (200 mL), dried over MgSO 4 and concentrated in vacuo to yield an oil (9.6 g). The oil was adsorbed with ethyl acetate-hexa (1: 1) and purified by flash chromatography on silica gel. The fractions containing the required product were collected, concentrated in vacuo and the remainder recrystallized from ethyl acetate-hexane to give a yellow solid of ethyl 1,2-dihydro-6- (trifluoromethoxy) -2- (tri-oluoro). Methyl) -3-quinolinecarboxylate (4.05 g, 32%) was calculated: mp 123-125 ° C. 1 H NMR (CDCl 3 , 300 MHz) 7.65 (s, 1H), 7.02 (m, 2H), 6.60 (m, 1H), 5.10 (m, 1H), 4.60 (brs, 1H), 4.28 (m, 2H) , 1.32 (t, 3H, J = 7.0 Hz). ESHRMS m / z 356.0698 (M−H, calculated 356.0721). Analytical Calcd C 14 H 11 NO 3 F 6 : C, 47.34; H, 3. 12; N, 3.94. Found: C, 47.37; H, 3.0 4; N, 3.93. Step 5. Preparation of 1,2-dihydro-6- (trifluoromethoxy) -2- (trifluoromethyl) -3-quinolinecarboxylic acid. Ethyl 1,2-dihydro-6- (trifluoromethoxy) -2- (trifluoromethyl) -3-quinolinecarboxylate and 2.5N aqueous sodium hydroxide (2 mL) in step 4 were added with methanol (15 mL) and water ( 15 mL). The solution was heated in a steam electrolyzer for 2 hours. The solution was cooled to rt and extracted with diethyl ether (50 mL). The aqueous phase was acidified with 3N NCl (pH = 1) and extracted with ethyl acetate (2 × 50 mL). The combined ethyl acetate extracts were dried over MgSO 4 and concentrated in vacuo to yield an oil. The oil was crystallized from cold dichloromethane-hexane and yellow needles of 1,2-dihydro-6- (trifluoromethoxy) -2- (trifluoromethyl) -3-quinolinecarboxylic acid (0.727 g, 89 %) Was calculated: mp 127.7-128.9 ° C. 1 H NMR (CDCl 3 , 300 MHz) 7.80 (s, 1 H), 7.05 (m, 2 H), 6.62 (d, 1 H, J = 8.0 Hz), 5.13 (m, 1H), 4.62 (brs. 1 H). ESHRMS m / z 326.0252 (M−H, calculated 326.0252). Analytical Calcd C 12 H 7 NO 3 F 6 : C, 44.05; H, 2. 16; N, 4.28. Found: C, 43.89; H, 2.04; N, 4.24. Example 163 6- (trifluoromethyl) -1,2-dihydro-2-trifluoromethyl-3-quinolinecarboxylic acid Step 1. Preparation of N- (4-trifluoromethylphenyl) -2,2-dimethylpropanamide. A solution of dichloromethane (200 mL), 4-aminobenzotrifluoride (32.0 g, 199 mmol) and triethyleneamine (40 g, 396 mmol) was cooled to 0 ° C. under dry nitrogen atmosphere. Trimethylacetyl chloride (32.9 g, 273 mmol) was added dropwise while maintaining below 10 ° C. After addition, the reaction was warmed to room temperature for 2 hours. The reaction was washed with water (2x200 mL) saturated ammonium chloride solution (2x200 Ml), dried over sodium sulfide and filtered. The solvent was removed in vacuo to yield N- (4-trifluoromethylphenyl) -2,2-dimethylpropanamide (48.0 g, 98%) as a white solid: mp 157-159 ° C. 1 H NMR (CDCl 3 , 300 MHz) 7.61 (ab, 4H, J = 8.7, Δν = 28.6 Hz), 7.47 (br s, 1H), 1.33 (s, 9H). ESHRMS m / z 246.1123 (M + H + , calculated 246.1106). Analytical Calcd C 12 H 14 F 3 NO: C, 58.77; H, 5.75; N, 5.71. Found: C, 58.28; H, 5.79; N, 5.65. Step 2. Preparation of N- [2-formyl-4- (trifluoromethyl) phenyl] -2,2-dimethyl propanamide. N- (4-trifluoromethylphenyl) -2,2-dimethyl propanamide (10.13 g, 414 mmol) and anhydrous THF (150 mL) were added to a 1 liter three necked round bottom flask equipped with a funnel, a magnetic stirrer and a temperature monitor. . The reaction was cooled to −78 ° C. under nitrogen and slowly added n-butyllithium (50 mL, 2.5 M in hexane, 124 mmol) for more than 0.5 h to ensure the temperature did not rise above −65 ° C. The contents were kept at -78 ° C for 1 hour and 0 ° C for 2 hours and then cooled back to -78 ° C. Excess N, N-dimethylformamide (100 mL, 1.37 mol) was added. The reaction was allowed to warm to rt and stirred for 2 h. Aqueous 1N HCl was added to the reaction until pH was 1. The reaction was washed with water (2x200 mL), saturated ammonium chloride solution (2x200 mL), dried over sodium sulfide and filtered. The filtrate was concentrated in vacuo to yield a yellow solid. The product was purified by flash chromatography (silica gel, 10% ethyl acetate, 90% hexane) and concentrated to the appropriate portion of solid N- (2-formyl-4-trifluoromethylphenyl) -2,20dimethylpropanamide (7.36 g). , 65%) was calculated: mp 69-73 ° C. 1 H NMR (CDCl 3 , 300 MHz) 11.5 (br s, 1H), 9.99 (s, 1H), 8.67 (d, 1H, J = 8.8 Hz), 7.94 (d, 1H, J = 1.6 Hz), 7.83 ( m, 1 H), 1.37 (s, 9 H). ESHRMS m / z 274.1060 (M + H + , calculated 274.1055). Analytical calculation C 13 H 14 F 3 NO 2 : C, 57.14; H, 5. 16; N, 5.13. Found: C, 57.15; H, 5. 43; N, 5.01. Step 3. Preparation of ethyl-6- (trifluoromethyl) -1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylate. To a dimethyl sulfoxide (10 mL) suspension of N- (2-formyl-4- (trifluoromethylphenyl) -2,2-dimethyl propanamide (step 2) (921 mg, 3.7 mol)) lithium hydride (115 mg, 14.5 mmol) Ethyl 4,4,4-trifluoro crotonate (2.83 g, 16.8 mmol) was added and the reaction heated to 30 ° C. for 4 h. After addition of ethyl acetate (50 mL), the reaction was washed with water (2 × 30 mL), saturated ammonium chloride solution (2 × 30 mL), dried over sodium sulfide and filtered. The filtrate was concentrated in vacuo to yield a yellow solid. The product was purified by flash chromatography (silica gel, adsorbent: ethyl acetate-hexane, 1: 9), and the appropriate portion concentrated to a yellow solid, ethyl-6-trifluoromethyl-1,2-dihydro-2- (tri Fluoromethyl) -3-quinolinecarboxylate (65 mg, 5%) was calculated: mp 138-139 ° C. 1 H NMR (CDCl 3 , 300 MHz) 7.67 (s, 1 H), 7.26 (s, 1 H), 7.04 (d, 1 H, J = 6.6 Hz), 6.62 (m, 1H), 5.14 (m, 1H), 4.60 (brs, 1 H), 4.32 (m, 2H), 1.35 (t, 3H, J = 7.0 Hz). ESHRMS m / z 338.0592 (M−H, calculated 338.0616). Analytical Calcd C 13 H 11 F 3 NO 2 : C, 49.57; H, 3. 27; N, 4.13; Found: C, 49.23; H, 2. 81; N, 3.93. Step 4. Preparation of ethyl-6-trifluoromethyl-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid. Ethyl 6-trifluoromethyl-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylate (45 mg, 0.13 mmol) of step 3 was added to methanol-THF-water (10 mL, 7: 2: 1). In suspension). Lithium hydroxide (24 mg, 0.52 mmol) was added and the mixture was gradually heated for reflux for 2 hours. The reaction was cooled to room temperature and 1N HCl was added until pH = 1. The organic solvent was provided in vacuo and yielded a yellow solid suspension. Diethyl ether (20 mL) was added and the solution was washed with water (2x20 mL), saturated ammonium sulfide (2x20 mL), dried over sodium sulfide and filtered. The filtrate was concentrated in vacuo to yield 6-trifluoromethyl-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid (0.041 g, 0.132 mmol, 99%) as a yellow solid. : mp 150-156 ° C. 1 H NMR (CD 3 OD, 300 MHz) 7.78 (s, 1 H), 7.48 (s, 1 H), 7.40 (m, 1 H), 6.81 (m, 1 H), 5.17 (m, 1 H). ESHRMS m / z 310.0307 (M−H, calculated 310.0303). Example 164 6-cyano-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid Step 1. Preparation of ethyl-6-cyano-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylate. N, N-dimethylformamide (5 mL) was degassed with nitrification for 30 minutes in a three necked round bottom flask with condenser, temperature monitor, nitrogen lowering, heating lid. Ethyl 6-iodo-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylate (Example 158) (0.522 g, 1.32 mmol) and zinc cyanide (0.102 g, 0.792 mmol) were added to N , N-dimethylformamide was added, and the mixture was stirred vigorously for 10 minutes. Tetrakis (triphenyl-phosphine) palladium (O) (0.068 g, 0.53 mmol) was added and heated gradually to 80 ° C. for 2 h under nitrogen atmosphere. Ethyl acetate (20 mL) was added followed by extraction with aqueous 2N ammonium hydroxide (2x10 mL), water (2x10 mL), saturated ammonium chloride (2x10 mL), dried over sodium sulfide and the solvent removed in vacuo to yield a yellow solid. The product was purified by flash chromatography (silica gel, ethyl acetate-hexane, 3: 1) and ethyl yellow-cyano-1,2-dihydro-2- (trifluoromethyl) as a yellow solid by concentration in the appropriate portion. -3-Quinolinecarboxylate (188 mg, 48%) was calculated: mp 211-212 ° C. 1 H NMR (CDCl 3 , 300 MHz) 7.68 (s, 1 H), 7.43 (m, 2 H), 6.69 (d, 1 H, J = 8.3 Hz), 5.22 (m, 1 H), 4.98 (br s, 1 H), 1.30 (m, 2H), 1.36 (t, 3H, J = 7.1 Hz). EIHRMS m / z 314.1147 (M + NH 4 + , calculated 314.1116). Analytical Calcd C 14 H 11 F 3 N 2 O 2 : C, 56.76; H, 3. 74; N, 9.46. Found: C, 56.44; H, 4.03; N, 9.29. Step 2. Preparation of 6-cyano-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid. Ethyl 6-cyano-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylate (140 mg, 0.45 mmol) was added to methanol-THF-water (10 mL, 7: 2: 1) and hydroxylated. Lithium (76 mg, 0.91 mmol) was added and the mixture was gradually heated for reflux for 2 hours. The reaction was cooled at room temperature and 1N aqueous hydrochloric acid was added until pH = 1. The suspension was yielded as a yellow solid with organic solvent removed in vacuo. Diethyl ether (20 mL) was added and the solution was washed with water (2x20 mL), saturated ammonium sulfide (2x20 mL), dried over sodium sulfide and filtered. The filtrate yielded a yellow solid, 6-cyano-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid (116 mg, 95%): mp 238-240 ° C. 1 H NMR (CD 3 OD / 300MHz) 7.75 (s, 1H), 7.56 (m, 1H), 7.43 (m, 1H), 6.79 (d, 1H, J = 8.5Hz), 5.19 (q, 1H, J = 7.1 Hz). EIHRMS m / z 267.0405 (M−H, calculated 267.0381). Analytical Calcd C 14 H 11 F 3 N 2 O 2 : C, 53.74; H, 2.63; N, 10.45. Found: C, 53.99; H, 2.89; N, 10.19. Example 165 6-chloro-1,2-dihydro-1-methyl-2- (trifluoromethyl) -3-quinolinecarboxylic acid Step 1. Preparation of ethyl 6-chloro-1,2-dihydro-1-methyl-2- (trifluoromethyl) -3-quinolinecarboxylate. Ethyl 6-chloro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylate (Example 157, step 2) (1.28 g, 4.21 mmol), tetrabutylammonium iodide (0.36 g, 0.92) mmol) and aqueous NaOH (50%, 2 mL) were vigorously stirred in methylene chloride (40 mL). Dimethyl sulfite (2.12 g, 16.84 mmol) was added to the dark orange mixture by injector for 2 hours. Hexane (5 mL) was added and the solution was washed with water (2x20 mL), saturated ammonium chloride solution, dried over sodium sulfide and filtered. The filtrate was concentrated in vacuo to yield an ester which was a yellow solid. The solid was purified by flash chromatography (silica gel, 50 g ethyl acetate-hexane, 1:19) and the appropriate portion concentrated to ethyl 6-chloro-1,2-dihydro-1-methyl-2- (trifluoromethyl ) -3-quinoline-carboxylate (1.2 g, 90% yield) was calculated: mp 118-120 ° C. 1 H NMR (CD 3 OD / 300MHz) 7.71 (s, 1H), 7.30-7.26 (m, 2H), 76.77-6.74 (m, 1H), 5.12 (q, 1H, J = 6.8 Hz), 4.44-4.22 (m, 2H), 3.18 (s, 3H), 1.35 (t, 3H, J = 7.0 Hz). EIHRMS m / z 320.0701 (M−H, calculated 320.0665). Analytical Calcd C 14 H 13 F 3 NO 2 Cl: C, 53.60; H, 4. 10; N, 4.38. Found: C, 52.57; H, 4. 14; N, 4.32. Step 2. Preparation of 6-chloro-1,2-dihydro-1-methyl-2- (trifluoromethyl) -3-quinolinecarboxylic acid. Ethyl 6-chloro-1,2-dihydro-1-methyl-2- (trifluoro-methyl) -3-quinolinecarboxylate (1.21 g, 3.78 mmol) was added to methanol-THF-water (20 mL, 7: 2: Suspended in 1). Lithium hydroxide (0.262 g, 6.24 mmol) was added and the mixture was gradually heated for reflux for 2 hours. The reaction was cooled at room temperature and 1N HCl was added until pH = 1. The organic solvent was removed in vacuo to yield a yellow solid suspension. Diethyl ether (20 mL) was added and the resulting solution was washed with water (2x20 mL), saturated ammonium chloride (2x20 mL), dried over sodium sulfide and filtered. The filtrate was concentrated in vacuo to yield 6-chloro-1,2-dihydro-1-methyl-2- (trifluoromethyl) -3-quinolinecarboxylic acid (1.08 g, 98% yield) as a yellow solid. Mp: 208-209 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.69 (d, 1H, J = 2.5 Hz), 7.28-7.24 (m, 2H), 6.73 (dd, 1H, J = 9.5, 2.5 Hz), 5.13 (q, 1H , J = 7.0 Hz), 3.16 (s, 3H). Analytical Calcd C 12 H 9 F 3 NO 2 Cl: C, 49.42; H, 3.11; N, 4.80; Cl, 12.16. Found: C, 49.88; H, 3. 29; N, 4.59; Cl, 12.42. Example 166 6-chloro-1,2-dihydro-2- (trifluoromethyl) -1-[[4- (trifluoromethyl) phenyl] methyl] -3-quinolinecarboxylic acid 1,2-dihydro-3-quinolinecarboxylic acid was prepared in a similar manner to that described in Example 165 above: mp 229-231 ° C. 1 H NMR (CD 3 OD / 300MHz) 7.77 (s, 1H), 7.58 (d, 2H, J = 8.0Hz), 7.39 (d, 2H, J = 8.0Hz), 7.30 (d, 1H, J = 2.4 Hz), 713 (dd, 1H, J = 8.9, 2.4 Hz), 6.75 (d, 1H, J = 8.9 Hz), 5.27 (q, 1H, J = 7.0 Hz), 4.90 (ab, 2H, J = 16.7 hz, Δν = 95.2 Hz). EIHRMS m / z 434.0401 (calculated MH 434.0383) Analytical calculated C 19 H 14 F 6 NO 2 Cl: C, 52.13; H, 3. 22; N, 3.22; Found: C, 52.36; H, 2.91; N, 3.21. Example 167 6-chloro-1-[(4-chlorophenyl) methyl] -1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid 1,2-dihydro-3-quinolinecarboxylic acid was prepared in a similar manner to that described in Example 165 above: mp 250-253 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.74 (s, 1 H), 7.32-7.13 (m, 6 H), 6.76 (d, 1 H, J = 8.7 Hz), 5.22 (q, 1H, J = 7.0 Hz), 4.81 (ab, 2H, J = 16.3 hz, Δν = 54.7 Hz). ESHRMS m / z 400.0105 (M−H, calculated 400.0119). Example 168 6-chloro-1,2-dihydro-2- (trifluoromethyl) -1-[[4- (methoxy) phenyl] methyl] -3-quinolinecarboxylic acid 1,2-dihydro-3-quinolinecarboxylic acid was prepared in a similar manner to that described in Example 165 above: mp 196-197 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.71 (s, 1H), 7.27-7.26 (m, 1H), 7.18-7.12 (m, H), 6.85-6.81 (m, 3H), 5.16 (q, 1H, J = 7.1 Hz), 4.69 (ab, 2H, J = 15.3 Hz, Δν = 111.8 Hz), 3.73 (s, 3H). ESHRMS m / z 396.0625 (M−H, calculated 396.0614). Analytical Calcd C 19 H 14 F 6 NO 2 Cl: C, 52.13; H, 3. 22; N, 3.22; Found: C, 52.36; H, 2.91; N, 3.21. Example 169 6-chloro-1-[(4-cyanophenyl) methyl] -1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid 1,2-dihydro-3-quinolinecarboxylic acid was prepared in a similar manner to that described in Example 165 above: mp 258-260 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.78 (s, 1 H), 7.66 (d, 2H, J = 8.2 Hz), 7.41 (d, 2H, J = 8.2 Hz), 7.33 (d, 1H, J = 2.7 Hz), 7.15 (dd, 1H, J = 8.7, 2.7 Hz), 6.71 (d, 1H, J = 8.7 Hz), 5.31 (q, 1H, J = 7.0 Hz), 4.94 (ab, 2H, J = 17.1 , Δν = 91.8 Hz). ESHRMS m / z 391.0443 (M−H, calculated 391.0461). Analytical Calcd C 19 H 12 F 3 N 2 O 2 Cl + 0.53% H 2 O: C, 57.79; H, 3.55; N, 7.09; Found: C, 57.26; H, 3. 17; N, 6.78. Example 170 6-chloro-1,2-dihydro-1-[(4-nitrophenyl) methyl] -2- (trifluoromethyl) -3-quinolinecarboxylic acid 1,2-dihydro-3-quinolinecarboxylic acid was prepared in a similar manner to that described in Example 165 above: mp 225-228 ° C. 1 H NMR (CD 3 OD-3% TFA / 300 MHz) 8.14 (d, 2H, J = 8.8 Hz), 7.77 (s, 1H), 7.42 (d, 2H, J = 8.8 Hz), 7.29 (d, 1H , J = 2.4 Hz), 7.11 (dd, 1H, J = 8.9, 2.4 Hz), 6.67 (d, 1H, J = 8.9 Hz), 5.27 (q, 1H, J = 6.8 Hz), 4.93 (ab, 2H , J = 17.2 Hz, Δν = 95.0 Hz). ESHRMS m / z 411.0327 (M−H, calculated 411.0359). Example 171 6-chloro-1,2-dihydro-1-ethyl-2- (trifluoromethyl) -3-quinolinecarboxylic acid 1,2-dihydro-3-quinolinecarboxylic acid was prepared in a similar manner to that described in Example 165 above: mp 201-202 ° C. 1 H NMR (CD 3 OD / 300 MHz) 7.67 (s, 1 H), 7.25-7.22 (m, 2 H), 6.86 (d, 1 H, J = 8.7 Hz), 5.21 (q, 1H, J = 7.0 Hz), 3.81-3.71 (m, 1H), 3.47-3.39 (m, 1H), 1.20 (t, 3H, J = 7.2 Hz). ESHRMS m / z 304.0360 (M−H, calculated 304.0352). Example 172 (s) -6-chloro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid To a solution of ethyl acetate (25 mL) and 6-chloro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid (Example 157) (6.75 g, 24.3 mmol) (-)-α-methylbenzylamine (1.50 g, 12.2 mmol) was added. Hexane (50 mL) was added to the resulting solution and mixed. Agitation was stopped and the reaction was left at room temperature for 16 hours while yellow crystals formed. The crystals were collected and washed with diethyl acetate-hexane (100 mL, 1: 2). The resulting yellow solid (932 mg) was dissolved in ethyl acetate (20 mL) and extracted with 1N HCl (3 × 10 mL). The organic phase was dried over sodium sulfide and removed by pressing the solvent. Yield as a yellow solid (648 mg, 10% yield) of (s) -6-chloro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid: mp 173-176 ° C. 1 H NMR (acetone-d 6 , 300 MHz) 7.80 (s, 1 H), 7.35 (d, 1 H, J = 2.2 Hz), 7.18 (d, 1H, J = 8.0, J = 2.2 Hz), 6.86 (d, 1H, J = 8.0 Hz), 6.60 (brs, 1H), 5.20 (m, 1H). Analytical Calcd C 11 H 7 NO 2 F 3 Cl C, 47.40 H, 2.54; N, 5.40. Found: C, 47.49; H, 2. 60; N, 4.98. The compound was found to have optical purity greater than 90% (excluding the error). Optical purity was determined by the HPLC described in Example 66 above. Example 173 6- (2,2,2-trifluoro-1-hydroxyethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid Step 1. Preparation of ethyl 6- (1-hydroxy-2,2,2-trifluoroethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylate. Aldehyde (Example 75, Step 1) (0.89 g, 3.0 mmol) was cooled to 0 ° C. and treated with a solution of 0.5 M trimethyl (trifluoromethyl) silane (8.4 mL, 4.2 mmol) and then 1.0 M tetrabutylammonium fluoride. Four drops of solution were added. The reaction was warmed to rt and stirred for 21.1 h. The reaction was cooled with 3N HCl, extracted with ethyl acetate, washed with water, brine, dried over MgSO 4 and concentrated in vacuo to yield a brown oil (1.02 g). The oil was adsorbed with 10% ethyl acetate / hexane to yield the purified on silica gel by flash chromatography brown oil (0.77g, 58%): 1 H NMR (CDCl 3 / 300MHz) 7.72 (d, 1H, J = 3.4 Hz), 7.34 (m, 2H), 6.99 (d, 1H, J = 8.5 Hz), 5.71 (q, 1H, J = 6.8 Hz), 4.83 (q, 1H, J = 6.4 Hz), 4.33 (m , 2H), 1.35 (t, 3H, J = 7.1 Hz), 0.11 (s, 9H). FABLRMS m / z 443 (M + H). Step 2. Preparation of 6- (1-hydroxy-2,2,2-trifluoroethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid. The ester in step 1 (0.15 g, 0.34 mmol) was dissolved in THF (2 mL) and ethanol (2 mL), treated with 2.5N NaOH (1 mL, 2.5 mmol) and stirred at room temperature for 18.6 hours. The reaction compound was concentrated in vacuo, acidified with 3N HCl and extracted with ethyl acetate, washed with 3N HCl, brine, dried over MgSO 4 and concentrated in vacuo to give a yellow oil which was recrystallized from ethyl acetate / hexanes to give white Calculated solid (0.03 g, 25%): mp 114-120 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.94 (s , 1H), 7.65 (s, 1H), 7.60 (dd, 1H, J = 8.2Hz 2.0Hz), 7.1 (d, 1H, J = 8.3Hz) , 5.87 (q, 1H, J = 7.0 Hz), 5.24 (q, 1H, J = 7.0 Hz). FABLRMS m / z 341 (mh). ESHRMS m / z 341.0241 (M−H, calculated 341.0249). Example 174 6-chloro-2- (trifluoromethyl) -1,2-dihydro [1,8] naphthyridine-3-carboxylic acid Step 1. Preparation of N- [5-chloropyridin-2-yl] -2,2-dimethylpropanamide. 2-amino-5-chloropyridine (10.0 g, 0.078 mol) (Aldrich) and triethylamine (12 mL, 0.086 mol) were added to methylene chloride (200 mL) at 0 ° C. and trimethylacetyl chloride in methylene chloride (15 mL) was added. Added dropwise. The reaction was allowed to warm overnight at room temperature with stirring. The resulting mixture was washed with water, brine, dried over MgSO 4 and filtered. The filtrate was concentrated in vacuo to yield a colorless oil (19.2 g). The oil was dissolved in hexane and cooled to precipitate a solid. The solid was obtained by filtration to yield the amide (14.96 g, 90%) as a white solid: mp 51.4-53.4 ° C. 1 H NMR (CDCl 3 / 300MHz ) 8.25-8.15 (m, 2H), 8.00 (br s, 1H), 7.68-7.60 (m, 1H), 1.28 (s, 9H). Analytical Calcd C 10 H 13 N 2 OCl: C, 56.47; H, 6. 16; N, 13.17 Found: C, 56.72; H, 6. 34; N, 12.88. Step 2. Preparation of N- [5-chloro-3-formylpyridin-2-yl] -2,2-dimethylpropanamide. Amide (step 1) (5.0 g, 0.024 mole) was added to THF (100 mL), the mixture was cooled to -78 ° C, and t-butyl lithium (1.7 M in pentane, 324 mL, 0.055 mole) was added dropwise. Dimethylformamide (2.3 mL, 0.03 mole) was added dropwise at −78 ° C. for 3 hours and the mixture was left at room temperature to warm. The reaction was immersed in ice water (200 mL) and extracted with ethyl acetate. The reaction organic phase was dried over MgSO 4 and concentrated in vacuo to a volume of 20 mL. The precipitated white solid was collected by filtration to yield a formylated product (3.24 g, 56%): mp 168.7-170.8 ° C. 1 H NMR (CDCl 3 / 300MHz ) 10.60 (br s, 1H), 9.88 (s, 1H), 8.57 (s, 1H), 8.00 (s, 1H), 1.28 (s, 9H). Analytical Calcd C 11 H 13 N 2 O 2 Cl: C, 54.89; H, 5. 44; N, 11.64 Found: C, 54.87; H, 5. 42; N, 11.40. Step 3. Preparation of 2-amino-5-chloro-3-formylpyridine. The product of step 2 (2.7 g, 11 mmol) and 3N HCl (50 mL) were heated to reflux for 2 hours. The reaction was cooled to room temperature and concentrated in vacuo to yield a pale yellow solid (2.1 g). The solid was partitioned between ethyl acetate and 2.5N NaOH solution. The ethyl acetate phase was dried over MgSO 4 and vacuum filtered to give a solid (1.7 g). The solid was recrystallized from ethyl acetate to yield the required substituted pyridine (1.2 g, 68%) which was yellow needle crystal: mp 176.1-177.3 ° C. 1 H NMR (CDCl 3 / 300MHz ) 9.80 (s, 1H), 8.21 (s, 1H), 7.75 (s, 1H), 6.75 (br s, 2H). Analytical Calcd C 6 H 5 N 2 OCl: C, 46.03; H, 3. 22; N, 17.89 Found: C, 45.90; H, 3. 24; N, 17.80. Step 4. Preparation of ethyl 6-chloro-2- (trifluoromethyl) -1,2-dihydro [1,8 [naphthyridine-3-carboxylate. Mix the substituted pyridine (1.7 g, 11 mmol), anhydrous potassium carbonate (3.0 g, 22 mmol) and ethyl 4,4,4-trifluorocrotonate (3.3 mL, 22 mmol) from step 3 with anhydrous dimethylformamide (20 mL) Heated to 80 ° C. for 2 hours. The reaction was cooled to room temperature and partitioned between ethyl acetate (100 mL) and water (100 mL). The aqueous phase was extracted with more ethyl acetate (100 mL). The combined organic extracts were washed with brine (100 mL), dried over MgSO 4 and concentrated in vacuo to yield a brilliant tan solid. The solid was triturated with diethyl ether to yield an ester (613 mg, 18%) as a yellow solid. A small amount was recrystallized from ethyl acetate for analytical data: mp 180.1-181.9 ° C. 1 H NMR (CDCl 3 / 300MHz ) 7.99 (s, 1H), 7.61 (s, 1H), 7.39 (s, 1H), 6.00 (br s, 1H), 95.33-5.20 (m, 1H), 4.40-4.23 (m, 2H), 1.40-1.30 (m, 3H). Analytical Calcd C 12 H 10 N 2 O 2 F 3 Cl: C, 47.00; H, 3. 29; N, 9.13 Found: C, 46.83; H, 3.03; N, 9.18. Step 5. Preparation of 6-chloro-2- (trifluoromethyl) -1,2-dihydro [1,8] naphthyridine-3-carboxylic acid. The ester of step 4 (1.3 g, 4.4 mmol) and 2.5 N sodium hydroxide solution (3.5 mL, 9 mmol) were mixed in THF (25 mL), methanol (10 mL) and water (25 mL). The mixture was heated at 50 ° C. for 4 hours, cooled to room temperature and then concentrated in vacuo to remove THF and methanol. The resulting aqueous solution was washed with diethyl ether (2 × 100 mL) and the aqueous phase was acidified with 3N HCl to yield a precipitate of yellow solid (1.1 g). The solid was triturated with ethanol-acetone to collect by vacuum filtration to give the title compound (276 mg, 23%) as a yellow solid: mp 287.4-288.4 ° C. 1 H NMR (acetone -d 6 / 300MHz) 11.50 (br s, 1H), 8.03 (s, 1H), 7.83 (s, 1H), 7.75 (s, 1H), 7.28 (br s, 1H), 5.42- 5.30 (m, 1 H). Analytical Calcd C 10 H 6 N 2 0 2 F 3 Cl: C, 43.11; H, 2. 17; N, 10.05 Found: C, 42.88; H, 2.03; N, 10.06. Example 175 Preparation of (s) -6,8-dichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid 6,8-Dichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid (Example 32) (300 g, 1.04 mol) was added to ethyl acetate (750 mL). The mixture was stirred for 5 minutes and then heated to 70 ° C. and held at this temperature for 5 minutes. The resulting product was cooled to 50 ° C. and (s)-(−)-α-methylbenzylamine (58 g, 0.48 mol) was added. Heptane (1880 mL) was added and the mixture was stirred for 0.5 h before the stirring was stopped. The reaction was cooled to 22 ° C. and left for 8 hours. The solid was washed with ethyl acetate-heptane (1: 3, 2x50 mL). The resulting solid was dried at 40 ° C. under vacuum for 24 hours to yield a salt (35 g, 16%). A 2 L three necked round bottom flask was rinsed with nitrogen and charged with deionized water (750 mL) and the salt (103 g, 0.24 mole) (this material was calculated by a similar procedure as described above). To obtain precipitated free carboxylic acid, concentrated HCl (37 mL) was added to the stirred suspension for 0.5 hours, stirred well below 20 ° C, stirred for 2 hours, the suspension was vacuum filtered and the solid was deionized water (5x50 mL). ) (Until the wash solution is neutral). The solid was dried under vacuum at 40 ° C. for 12 hours to yield the title compound (74 g, 100%) as a solid: mp 166.0-168.4 ° C. 1 H NMR (acetone -d 6 / 300MHz) 7.94 (s , 1H), 7.60 (s, 2H), 6.04 (q, 1H, J = 6.8Hz). ESHRMS m / z 310.9489 (MH, calculated 310.9450). The compound was found to have optical purity higher than 90% (excluding the error). Optical purity was found by the method described in Example 66 above. Rat Carrageenan Foot Pad Edema Test Carrageenan foot edema tests were performed with the materials, reactants and procedures described essentially in Winter et al. (Prog. Soc. Exp. Biol. Med., 111, 544 (1962)). Male rats were selected from each group for as similar average weight as possible. Rats were starved for water for 16 hours before the experiment. Mice were administered suspension compounds or media only orally (1 mL) in a vehicle containing 0.5% methyl cellulose and 0.025% surfactant. One hour later, a subcutaneous infusion of the sole of a carrageenan 1% solution / sterilized 1% 0.9% saline solution was performed and the volume of the administered foot was measured by a displacement plethysmometer with a digital indicator and a pressure transducer. The average foot swelling in the group of drug-treated animals was compared to that in the placebo-treated group and the percentage of edema inhibition was determined (Otterness and Bliven, Laboratory Models for Testing NSAIDs, in Non-steriadal Anti-inflammatory Drugs, (J. Lombardono, ed. 1985)). The percent inhibition shows the percent reduction from the control of the foot volume determined in this procedure and from the data of any compound of the invention summarized in Table I. Table I. Rat Foot Edema Loss of Pain % Suppression% Suppression Example 30 mg / kg body weight @ 30 mg / kg 1 57 58 ______________________________________________________________ Expression of in vivo activity of COX-1 and COX-2 Compounds of the invention exhibit in vivo inhibition of COX-2. Inhibition of the COX-2 inhibitory activity of the compounds of the present invention is described in the examples determined by the following method. a. Preparation of Recombinant COX Baculovirus Recombinant COX-1 and COX-2 were synthesized by Gierse et al. [J. Biochem., 305, 479-84 (1995). To generate baculovirus transfer vectors for COX-1 and COX-2, a 2.0kb fragment containing the genetic code portion of human or rat COX-1 or human or rat COX-2 was prepared by DR O'Reilly et al. The BamH1 portion of the baculovirus transfer vector pVL1393 (Invitrogen) was cloned in a similar manner to the method. Recombined baculovirus was isolated by transferring from 4 μg of baculovirus transfer vector DNA to SF9 insect cells (2 × 10 8 ) with 200 ng of the baculovirus plasmid linearized with calcium phosphate. MD Summers and GESmith, A Mannual of Methods for Baculovirus Vectors and Insect Cell Culture Procedures, Texas Agric. Exp. Station Bull. See 1555 (1987). Recombined virus was purified by three round plaque purification and a high drop (10 7 -10 8 pfu / mL) virus group was prepared. For production of large units, SF9 insect cells were injected into a 10 liter culture vessel (0.5 × 10 6 / mL) with a group of recombinant baculoviruses such as 0.1 injection duplication. After 72 hours the cells were centrifuged and the rounded cell population was tris / Sucrose (50 mM: 25%, containing 1% 3-[(3-Clamidopropyl) dimethylammonio] -1-propanesulfonate (CHAPS), pH 8.0). The homogenized was centrifuged at 10,000 × G for 30 minutes and the synthesized suspension was stored at −80 ° C. before COX activity was analyzed. b. Activity analysis of COX-1 and COX-2 COX activity was analyzed by PGE 2 / μg protein / hour formed using ELISA to track the released prostaglandins. Insect cell membranes containing CHAPS containing appropriate COX enzymes were incubated in potassium phosphate buffer (50 mM, pH 8.0) containing epinephrine, phenol and heme with the addition of arachidonic acid. The compound was preincubated with the enzyme for 10-20 minutes prior to the addition of arachidonic acid. At 37 ° C./room temperature, 40 μl of the reaction compound was transferred to 160 μl ELISA buffer and 25 μM indomesacin, and 10 minutes later, any reaction between arachidonic acid and the enzyme was stopped. PGE 2 formed was measured by standard ELISA technique (Cayman Chemical). The results are shown in Table II. c. Fast analysis of COX-1 and COX-2 activity COX activity was analyzed by PGE2 / μg protein / hour formed using ELISA to track the prostaglandin released. Insect cell membranes in which CHAPS containing appropriate COX enzymes were dissolved were incubated with 20 μl (10 μM) of 100 μM arachidonic acid in potassium phosphate buffer (0.05 M potassium phosphate, pH7.5, 2 μM phenol, 1 μM heme, 300 μM epinephrine). The compound was previously incubated with enzyme at 25 ° C. for 10 minutes before the addition of arachidonic acid. At 37 ° C./room temperature, 40 μl of the reaction compound was transferred to 160 μl ELISA buffer and 25 μM indomesacin, and 2 minutes later, any reaction between arachidonic acid and the enzyme was stopped. PGE 2 formed was measured by standard ELISA technique (Cayman Chemical). The results are shown in Table II. Table II. Example COX-2 * COX-1 * COX-2 COX-1 IC 50 μM IC 50 μM IC 50 μM IC 50 μM 1 0.3 45 2 <0.1 78 <0.1 50 6 <0.1> 100 7 0.1 16 <0.1 1.0 8 <0.1 61 <0.1 21 9 <0.1 1.4 <0.1 <0.1 12 7 55 13 .3 ＞ 100 14 ＞ 100 ＞ 100 15> 0.1 11 133.6 44 16 <0.1 24 1.4 51 18 12> 100 21 11 3.5 22 ＞ 100 ＞ 100 23 7 ＞ 100 24 ＞ 100 25> 100 78 Table II. continue Example COX-2 * COX-1 * COX-2 COX-1 IC 50 μM IC 50 μM IC 50 μM IC 50 μM 26> 100 20 27 67> 100 29 <0.1> 100 30 <0.1 1.2 16 3.8 31 <0.1 94 32 0.3 31 0.3 0.7 33 <0.1 5.7 8.2 28 35 2.2 8.9 1.7 11 38 0.2 6.2 25.7 57 39 0.2 45 1.3 ＞ 100 40 <0.1 24 74 43 42 <0.1 2.3 <0.1 11 43 99 85 44 0.3 72 21> 100 45 0.2 47 46> 100 46 0.2 24 74 43 Table II. continue Example COX-2 * COX-1 * COX-2 COX-1 IC 50 μM IC 50 μM IC 50 μM IC 50 μM 47 1.9 31 1.7 ＞ 100 49 24 ＞ 100 31 ＞ 100 50 79> 100 52 20> 100 52 8 13 6> 100 54 19> 100 55 46 ＞ 100 53 ＞ 100 56 12 ＞ 100 29 ＞ 100 57 21 10 21> 100 59 43> 100 65 <0.1 1.0 66 82 38 <0.1 16.9 67 <0.1 31 <0.1 6.7 81 <0.1 10.5 <0.1 1.6 82 <0.1 16 <0.1 5.6 83 <0.1 9.6 <0.1 1.4 Table II. continue Example COX-2 * COX-1 * COX-2 COX-1 IC 50 μM IC 50 μM IC 50 μM IC 50 μM 84 0.1 25 <0.1 2.8 88 <0.1 12.4 <0.1 6.4 91 <0.1 23 0.2 36 96 0.2> 100 0.3 100 97 0.2 78 0.1 25 98 2.0> 100 1.5 19 99 0.2 36 <0.1 23 101 <0.1 18 <0.1 16 103 36 61 104 <0.1 24 <0.1 8.2 105 0.3 4.5 0.2 0.1 106 0.2 21 <0.1 5.7 114 <0.1 <0.1 <0.1 <0.1 115 <0.1 <0.1 <0.1 <0.1 116 <0.1 <0.1 <0.1 <0.1 120 <0.1 98 <0.1 33 Table II. continue Example COX-2 * COX-1 * COX-2 COX-1 IC 50 μM IC 50 μM IC 50 μM IC 50 μM 125 <0.1 0.2 <0.1 <0.1 129 0.2 2.6 <0.1 0.3 138 0.3 42.5 <0.1 11.1 152 <0.1 74 <0.1 10 154 0.5 68.5 <0.1 37 155 <0.1 1.6 <0.1 <0.1 156 <0.1 0.8 <0.1 0.1 * Quick analysis Also included herein are one or more non-toxic, pharmacologically acceptable mediators and / or diluents and / or adjuvants (collectively referred to herein as “mediator” substances), and, preferably, in connection with other active ingredients. A group of pharmacological ingredients comprising the active compound of formula (I). The active compounds of the present invention may be administered by any suitable method and are preferably the form of pharmacological composition suitable for the method and the effective administration for the intended treatment. The active compound and the composition will be administered, eg, orally, intravenously, subcutaneously, intramuscularly or topically. The phrase “combination therapy” (or “combination therapy”), which implies the use of cyclooxygenase-2 inhibitors and other pharmacological agents, provides for each agent in a continuous manner in the diet that will provide the beneficial effect of the combination drug. It is meant to include the administration of, and consequently to include multi-administration of such agents in the same way as a single capsule of a fixed ratio of such active agents, or as separate capsules of each agent. The phrase “therapeutically effective” is intended to determine the amount of each agent and the frequency for the treatment of each agent itself that achieves the goal of improving the severity of the disease, while avoiding the side effects associated with alternative treatments. For oral administration, the pharmaceutical component is, for example, a tablet, capsule, suspension or liquid. The pharmaceutical ingredient is preferably in the form of a dosage unit comprising a specific amount of the active ingredient. Examples of such dosage units are tablets or capsules. The active ingredient is administered, for example, by infusion in a composition in saline, dextrose or water used as a suitable carrier. The amount of therapeutically active compound administered with the compound or composition of the present invention and the method of administration to treat the disease include age, weight, sex and medical condition of the subject, the severity of the disease, the method and frequency of administration, the particular compound consumed, and the like. It depends on many different factors. The pharmacological composition includes the range of about 0.1 to 2000 mg, preferably the range of about 0.5 to 500 mg, most preferably the range of about 1 to 100 mg. The daily dosage is suitably between about 0.01 and 100 mg / kg body weight, preferably between about 0.5 and 20 mg / kg body weight and most preferably between 0.1 and 10 mg / kg body weight. Daily administration can be administered in one to four doses daily. In case of psoriasis and other skin conditions, it may be desirable to apply topical treatment of the compounds of the invention to two to four affected areas daily. In case of inflammation of the eye or other surgical tissue, eg mouth and skin, the prescription is preferably for example 0.075 to 30% w / w, preferably 0.2 to 20% w / w, and preferably preferably 0.4 Application as a topical ointment or cream or suppository comprising the active ingredient for a total amount of 15% w / w. If prescribed as an ointment, the active ingredient will be used as a cream preparation that is easy to mix with paraffinic or water. Alternatively, the active ingredient will be formed into a cream which is a cream medicine of oil-and-water. Hopefully, the aqueous phase of the cream medicament comprises, for example, at least 30% w / w of a polyhydric alcohol such as propylene glycol, butane-1,3-diol, mannitol, sorbitol, giliserol, polyethylene glycol and mixtures thereof. Topical forms include compounds that enhance absorption or invasion of the active ingredient through the skin or other lesions. Examples of such skin absorption enhancers include analogous compounds associated with dimethyl sulfoxide. The compounds of the present invention can also be administered by transdermal devices. Preferably, topical administration will be achieved with a reservoir and porous membrane type or various solid based patches. In either case, the active agent is a fixed, permeable active agent attached to the skin or mucosal layer that is continuously delivered from the reservoir or microcapsules through the membrane. If the active agent is absorbed through the skin, a controlled and predetermined flow of active agent is administered to the subject. In the case of microcapsules, the encapsulated medicament also acts as a membrane. The oil phase of the emulsion of the present invention consists of a component known by known methods. If the phase comprises only emulsifiers, it comprises a compound of at least one fat or oil or of both fat and oil. Preferably, the hydrophilic emulsifier includes both lipophilic emulsifiers that act as stabilizers. It is also desirable to include both oils and fats. Emulsifiers with or without stabilizers are made of so-called emulsifying waxes, and the waxes together with oils and fats form emulsifying cream mains that form the so-called creamy oily dispersed phase. Suitable emulsifiers and emulsion stabilizers for use in the compositions of the present invention include Tween 60, Span 80, cetostearyl alcohol, myristyl alcohol, glyceryl monostearate, sodium lauryl sulfate, and the like. The choice of the appropriate oil or fat for the composition depends on the choice of the desired cosmetic ingredient, since the aqueous properties of the active compounds of most oils used pharmacologically as emulsifying ingredients are very low. Therefore, the cream is preferably a fat-free, stain-free, washable product at an appropriate concentration to avoid the weakness of tubes or other containers. Such as di-isoadiate, isocetyl stearate, propylene glycol diesters of coconut fatty acids, isopropyl myristate, decyl oleate, isopropyl parmitate, butyl stearate, 2-ethylhexyl parmitate or branched esters Straight or branched chain, short or dibasic esters are used. These may be used alone or in combination depending on the properties required. Alternatively, lipids with high melting points such as white soft paraffin and / or liquid paraffin or mineral oils are used. Suitable forms for topical administration of the eye also include tears wherein the active ingredient is dissolved or suspended in a suitable carrier, especially a liquid solvent for the active ingredient. The anti-inflammatory active ingredient is preferably present in the composition at a concentration of 0.5 to 20%, advantageously 0.5 to 10% and especially about 1.5% w / w. For therapeutic purposes, the active compound of the present invention is usually combined with adjuvant appropriate for the method in which one or more dosages are indicated. If administered to bone, the compound may contain lactose, sucrose, starch powder, cellulose esters of alkanoic acid, cellulose alkyl esters, talc, stearic acid, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric acid and sulfuric acid, gelatin, It is mixed with acacia rubber, sodium alginate, polyvinylpyrrolidone and / or polyvinyl alcohol for tablets or capsules for convenient administration. The capsule or tablet comprises a controlled-release form which is provided for the dispersion of the active compound in hydroxypropylmethyl cellulose. The form for parenteral administration is a sterile infusion solution or suspension of aqueous or non-aqueous isotonic. Such solutions and suspensions are prepared from sterile powders or granules with one or more carriers or diluents mentioned for use in the form for oral administration. The compound is dissolved in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride and / or various buffers. Other adjuvant and dosage forms are well and widely known in the pharmacological arts. All references mentioned are incorporated by reference as described herein. The prior document, USSN 60 / 044,485, is also described by reference. Although the present invention refers to the detailed embodiments, the details of the embodiments are not to be construed as limiting.
权利要求:
Claims (38) [1" claim-type="Currently amended] Benzopyran derivative compounds for treating inflammation, which are of Formula I 'or an isomer or a pharmacologically acceptable salt thereof; Wherein X is selected from O, S, CR c R b and NR a ; Wherein R a is selected from hydrido, C 1 -C 3 -alkyl, (optionally substituted phenyl) -C 1 -C 3 -alkyl, acyl and carboxy-C 1 -C 6 -alkyl; Wherein R b and R c are each hydrido, C 1 -C 3 -alkyl, phenyl-C 1 -C 3 -alkyl, C 1 -C 3 -perfluoroalkyl, chloro, C 1 -C 6 -alkyl Independently selected from thio, C 1 -C 6 -alkoxy, nitro, cyano and cyano-C 1 -C 3 -alkyl; Wherein R is selected from carboxyl, aminocarbonyl, C 1 -C 6 -alkylsulfonylaminocarbonyl and C 1 -C 6 -alkoxycarbonyl; Wherein R ″ is selected from hydrido, phenyl, thienyl and C 2 -C 6 -alkenyl; Wherein R 1 is from C 1 -C 3 -perfluoroalkyl, chloro, C 1 -C 6 -alkylthio, C 1 -C 6 -alkoxy, nitro, cyano and cyano-C 1 -C 3 -alkyl Selected; Wherein R 2 is hydrido, halo, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, halo-C 2 -C 6 -alkynyl, aryl- C 1 -C 3 -alkyl, aryl-C 2 -C 6 -alkynyl, aryl-C 2 -C 6 -alkenyl, C 1 -C 6 -alkoxy, methylenedioxy, C 1 -C 6 -alkylthio , C 1 -C 6 -alkylsulfinyl, aryloxy, arylthio, arylsulfinyl, heteroaryloxy, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkyl Oxy, heteroaryl-C 1 -C 6 -alkyloxy, aryl-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -haloalkoxy, C 1 -C 6 -haloalkylthio, C 1 -C 6 -haloalkylsulfinyl, C 1 -C 6 -haloalkylsulfonyl, C 1 -C 3- (haloalkyl-C 1 -C 3 -hydroxy Alkyl, C 1 -C 6 -hydroxyalkyl, hydroxyimino-C 1 -C 6 -alkyl, C 1 -C 6 -alkylamino, arylamino, aryl-C 1 -C 6 -alkylamino, heteroarylamino , Heteroaryl-C 1 -C 6 -alkylamino, nitro, cyano, amino, aminosulfonyl, C 1 -C 6 -alkylaminosulfonyl, arylaminosulfonyl, heteroarylaminosulfonyl, aryl-C 1 -C 6 -alkylaminosulfonyl, heteroaryl-C 1 -C 6 -alkylaminosulfonyl, heterocyclylsul Ponyl, C 1 -C 6 -alkylsulfonyl, aryl-C 1 -C 6 -alkylsulfonyl, optionally substituted aryl, optionally substituted heteroaryl, aryl-C 1 -C 6 -alkylcarbonyl, heteroaryl- C 1 -C 6 -alkylcarbonyl, heteroarylcarbonyl, arylcarbonyl, aminocarbonyl, C 1 -C 6 -alkoxycarbonyl, formyl, C 1 -C 6 -haloalkylcarbonyl and C 1 -C One or more radicals independently selected from 6 -alkylcarbonyl; and Wherein the A ring atoms A 1 , A 2 , A 3 , and A 4 are independently selected from carbon and nitrogen provided that at least two of A 1 , A 2 , A 3 and A 4 are carbon; Or R 2 together with ring A form a radical selected from naphthyl, quinolyl, isoquinolyl, quinolizinyl, quinoxalinyl and dibenzofuryl. [2" claim-type="Currently amended] The compound of claim 1, wherein X is O, S, CR c R b and NR a ; Wherein R a is hydrido, C 1 -C 3 -alkyl, (optionally substituted phenyl) -C 1 -C 3 -alkyl, acyl and carboxy-C 1 -C 6 -alkyl; R b and R b are each hydrido, C 1 -C 3 -alkyl, phenyl-C 1 -C 3 -alkyl, C 1 -C 3 -perfluoroalkyl, chloro, C 1 -C 6 -alkylthio, Independently selected from C 1 -C 6 -alkoxy, nitro, cyano and cyano-C 1 -C 3 -alkyl; Wherein R is selected from carboxyl, aminocarbonyl, C 1 -C 6 -alkylsulfonylaminocarbonyl and C 1 -C 6 -alkoxycarbonyl; wherein R ″ is hydrido, phenyl, thienyl And C 2 -C 6 -alkenyl, wherein R 1 is C 1 -C 3 -perfluoroalkyl, chloro, C 1 -C 6 -alkylthio, C 1 -C 6 -alkoxy, nitro, cya Iso and cyano-C 1 -C 3 -alkyl; R 2 is hydrido, halo, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl , halo, -C 2 -C 6 - alkynyl, aryl -C 1 -C 3 - alkyl, aryl, -C 2 -C 6 - alkynyl, aryl, -C 2 -C 6 - alkynyl, C 1 -C 6 - Alkoxy, methylenedioxy, C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfinyl, aryloxy, arylthio, arylsulfinyl, heteroaryloxy, C 1 -C 6 -alkoxy-C 1- C 6 -alkyl, aryl-C 1 -C 6 -alkoxy, heteroaryl-C 1 -C 6 -alkyloxy, aryl-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 - haloalkyl alkoxyl , C 1 -C 6 - haloalkyl thio, C 1 -C 6 - haloalkyl sulfinyl, C 1 -C 6 - haloalkyl sulfonyl, C 1 -C 3 - (haloalkyl, -C 1 -C 3 - hydroxy Oxyalkyl, C 1 -C 6 -hydroxyalkyl, hydroxyamino-C 1 -C 6 -alkyl, C 1 -C 6 -alkylamino, arylamino, aryl-C 1 -C 6 -alkylamino, heteroaryl Amino, heteroaryl-C 1 -C 6 -alkylamino, nitro, cyano, amino, aminosulfonyl, C 1 -C 6 -alkylaminosulfonyl, arylaminosulfonyl, heteroarylaminosulfonyl, aryl-C 1- C 6 -alkylaminosulfonyl, heteroaryl-C 1 -C 6 -alkylaminosulfonyl, heterocyclylsulfonyl, C 1 -C 6 -alkylsulfonyl, aryl-C 1 -C 6 -alkylsulfonyl , Optionally substituted aryl, optionally substituted heteroaryl, aryl-C 1 -C 6 -alkylcarbonyl, heteroaryl-C 1 -C 6 -alkylcarbonyl, heteroarylcarbonyl, arylcarbonyl, aminocarbonyl, C 1 -C 6 - alkoxycarbonyl, formyl, C 1 -C 6 - haloalkenyl Of the A ring atoms in the A 1, A 2, A 3 , and A 4 is A 1, A 2, A 3 , and A 4; alkyl and the one or more radicals selected from carbonyl-carbonyl and C 1 -C 6 Independently selected from carbon and nitrogen provided that at least three are carbon; Or R 2 is a compound of formula (I ′) or an isomer or pharmacologically acceptable salt thereof that forms together with ring A a naphthyl or quinolyl radical. [3" claim-type="Currently amended] The compound of claim 2, wherein X is selected from O, S, and NR a ; wherein R a is selected from hydrido, C 1 -C 3 -alkyl and (optionally substituted phenyl) methyl; In which R ″ is selected from hydrido and C 2 -C 6 -alkenyl; wherein R is carboxyl; wherein R 1 is selected from C 1 -C 3 -perfluoroalkyl; wherein R 2 Is hydrido, halo, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, halo-C 2 -C 6 -alkynyl, phenyl-C 1 -C 6 -alkyl, phenyl-C 2 -C 6 -alkynyl, phenyl-C 2 -C 6 -alkenyl, C 1 -C 3 -alkoxy, methylenedioxy, C 1 -C 3 -alkoxy-C 1 -C 3 -alkyl, C 1 -C 3 -alkylthio, C 1 -C 3 -alkylsulfinyl, phenyloxy, phenylthio, phenylsulfinyl, C 1 -C 3 -haloalkyl-C 1 -C 3 -hydroxy Alkyl, phenyl-C 1 -C 3 -alkyloxy-C 1 -C 3 -alkyl, C 1 -C 3 -haloalkyl, C 1 -C 3 -haloalkoxy, C 1 -C 3 -haloalkylthio, C 1 -C 3 -hydroxyalkyl, C 1 -C 3- Alkoxy-C 1 -C 3 -alkyl, hydroxyamino-C 1 -C 3 -alkyl, C 1 -C 6 -alkylamino, nitro, cyano, amino, aminosulfonyl, N-alkylaminosulfonyl, N -Arylaminosulfonyl, N-heteroarylaminosulfonyl, N- (phenyl-C 1 -C 6 -alkyl) aminosulfonyl, N- (heteroaryl-C 1 -C 6 -alkyl) aminosulfonyl, phenyl -C 1 -C 3 - alkylsulfonyl, 5- to 8-membered heterocyclic ilsul sulfonyl, C 1 -C 6 - alkylsulfonyl, optionally substituted phenyl, optionally substituted 5- to 9-membered heteroaryl, phenyl -C 1 -C 6 -alkylcarbonyl, phenylcarbonyl, 4-chlorophenylcarbonyl, 4-hydroxyphenylcarbonyl, 4-trifluoromethylphenylcarbonyl, 4-methoxyphenylcarbonyl, aminocarbonyl, One or more radicals independently selected from formyl, and C 1 -C 6 -alkylcarbonyl; wherein the A ring atoms A 1 , A 2 , A 3 and A 4 are selected from A 1 , A 2 , A 3 and A 4 ; At least three are carbon As to, it is independently selected from carbon and nitrogen; R 2 is a benzopyran derivative compound for the treatment of inflammation which is a compound of formula (I ′) or an isomer or a pharmacologically acceptable salt thereof which forms together with ring A a naphthyl, benzofurylphenyl or quinolyl radical. [4" claim-type="Currently amended] The compound of claim 3, wherein X is selected from O, S and NR a ; wherein R a is hydrido, methyl, ethyl, (4-trifluoromethyl) benzyl, (4-chloromethyl) benzyl, (4-methoxy) benzyl, and (4-cyano) benzyl, (4-nitro) benzyl; wherein R is carboxyl; wherein R "is selected from hydrido and ethenyl; Wherein R 1 is selected from trifluoromethyl and pentafluoroethyl; wherein R 2 is hydrido, chloro, bromo, fluorine, iodo, methyl, t-butyl, ethenyl, ethynyl, 5-chloro -1-pentynyl, 1-pentynyl, 3,3-dimethyl-1-butynyl, benzyl, phenylethyl, phenyl-ethynyl, 4-chlorophenyl-ethynyl, 4-methoxyphenyl-ethynyl, phenyl Ethenyl, methoxy, methylthio, methylsulfinyl, phenyloxy, phenylthio, phenylsulfinyl, methylenedioxy, benzyloxymethyl, trifluoromethyl, difluoromethyl, pentafluoroethyl, tripleru Lemethoxy, trifluoromethylthio, hydroxymethyl, hydroxy-trifluoroethyl, methoxymethyl, hydroxyiminomethyl, N-methylamino, nitro, cyano, amino, aminosulfonyl, N-methylaminosulfonyl , N-phenylaminosulfonyl, N-furylaminosulfonyl, N- (benzyl) aminosulfonyl, N- (furylmethyl) aminosulfonyl, benzylsulfonyl, phenylethylaminosulfonyl, furylsulfonyl, methylsul Phenyl, benzimidazolyl, thienyl, chloro, furyl, chloro-substituted furyl, benzylcarbonyl substituted with one or more radicals selected from phonyl, phenyl, chloro, fluorine, bromo, methoxy, methylthio and methylsulfonyl At least one radical independently selected from optionally substituted phenylcarbonyl, aminocarbonyl, formyl and thienyl substituted with methylcarbonyl; wherein the A ring atoms A 1 , A 2 , A 3 and A 4 are A 1; one, A 2, A 3 and A 4 at least The dog to the condition that a carbon selected from carbon and nitrogen, and; R 2 is a ring A and with naphthyl or quinolyl possible Formula I 'compounds or isomers, or pharmaceutically acceptable of forming a radical salt thereof benzo for the treatment of inflammation Pyran derivative compounds. [5" claim-type="Currently amended] The benzopyran derivative compound for treating inflammation according to claim 4, wherein the compound is selected from the following compounds and their isomers or pharmacologically acceptable salts thereof; 6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 2,7-bis (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 7-bromo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-7-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8- (1-methylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-7- (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (1-methylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-ethoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7- (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-bromo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-bromo-6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-trifluoromethoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 5,7-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7,8-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7-isopropyloxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-phenyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7,8-dimethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-bis (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7- (1-methylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7-phenyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-7-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-7-phenyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,7-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-dibromo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-dimethoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-nitro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-amino-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; Ethyl 6-amino-2-trifluoromethyl-2H-1-benzopyran-3-carboxylate; 6-chloro-8-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-chloro-6-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-chloro-6-methoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-difluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-bromo-8-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-bromo-6-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-bromo-6-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-bromo-5-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-bromo-8-methoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7- (N, N-diethylamino) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[[(phenylmethyl) amino] sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[(dimethylamino) sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-aminosulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6- (methylamino) sulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[(4-morpholino) sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[(1,1-dimethylethyl) aminosulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[(2-methylpropyl) aminosulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-methylsulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-chloro-6-[[(phenylmethyl) amino] sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-N, N-diethylaminosulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-phenylacetyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6- (2,2-dimethylpropylcarbonyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-dichloro-7-methoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[[(furanylmenyl) amino] sulfonyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-[(phenylmethyl) sulfonyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-[[(phenylethyl) amino] sulfonyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-iodo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-iodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 8-bromo-6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-formyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-formyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-bromo-7- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 5,6-dichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-cyano-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-hydroxymethyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (difluoromethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 2,6-bis (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 5,6,7-trichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6,7,8-trichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (methylthio) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (methylsulfinyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 5,8-dichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (pentafluoroethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 2- (trifluoromethyl) -6-[(trifluoromethyl) thio] -2H-1-benzopyran-3-carboxylic acid; 6,8-dichloro-7-methyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-2,7-bis (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 5-methoxy-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-benzoyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (4-chlorobenzoyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (4-hydroxybenzoyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-phenoxy-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 8-chloro-6- (4-chlorophenoxy) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 2- (trifluoromethyl) -6- [4- (trifluoromethyl) phenoxy) -2H-1-benzopyran-3-carboxylic acid; 6- (4-methoxyphenoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (3-chloro-4-methoxyphenoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (4-chlorophenoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 8-chloro-2- (trifluoromethyl) -6- [4- (trifluoromethyl) phenoxy] -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-cyano-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-[(hydroxyimino) methyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (hydroxymethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 8- (1H-benzimidazol-2-yl) -6-chloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 7- (1,1-dimethylethyl) -2- (pentafluoroethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (methoxymethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (benzyloxymethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-ethenyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-ethynyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (2-thienyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (2-furanyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (5-chloro-1-pentynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (1-pentynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (phenylethynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (3,3-dimethyl-1-butynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-[(4-chlorophenyl) ethynyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-[(4-methoxyphenyl) ethynyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (phenylethynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (4-chlorophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (3-methoxyphenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-[(4-methylthio) phenyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-[(4-methylsulfonyl) phenyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-phenyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-bromo-8-fluoro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (4-fluorophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-phenyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 8-chloro-6-fluoro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6,8-diiodo-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (5-chloro-2-thienyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (2-thienyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (4-chlorophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (4-bromophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (ethynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-methyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (4-methoxyphenyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-2- (trifluoromethyl) -4-ethenyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-2- (trifluoromethyl) -4-phenyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-4- (2-thienyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (2,2,2-trifluoro-1-hydroxyethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 6,8-dimethyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 6- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 7-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 6,7-dimethyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 8-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 6-chloro-7-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 7-chloro-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 6,7-dichloro-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 2- (trifluoromethyl) -6-[(trifluoromethyl) thio] -2H-1-benzothiopyran-3-carboxylic acid; 6,8-dichloro-2-trifluoromethyl-2H-1-benzothiopyran-3-carboxylic acid; 6-chloro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6,8-dichloro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6,7-difluoro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-iodo-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-bromo-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 1,2-dihydro-6- (trifluoromethoxy) -2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6- (trifluoromethyl) -1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-cyano-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-chloro-1,2-dihydro-1-methyl-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-chloro-1,2-dihydro-2- (trifluoromethyl) -1-[[4- (trifluoromethyl) phenyl] methyl] -3-quinolinecarboxylic acid; 6-chloro-1-[(4-chlorophenyl) methyl] -1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-chloro-1,2-dihydro-2- (trifluoromethyl) -1-[[4- (methoxy) phenyl] methyl] -3-quinolinecarboxylic acid; 6-chloro-1-[(4-cyanophenyl) methyl] -1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-chloro-1,2-dihydro-1-[(4-nitrophenyl) methyl] -2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-chloro-1,2-dihydro-1-ethyl-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-chloro-2- (trifluoromethyl) -1,2-dihydro [1,8] naphthyridine-3-carboxylic acid; 2-trifluoromethyl-2H-naphtho [1,2-b] pyran-3-carboxylic acid; 2-trifluoromethyl-3H-naphtho [2,1-b] pyran-3-carboxylic acid; 2-trifluoromethyl-2H-naphtho [2,3-b] pyran-3-carboxylic acid; 5- (hydroxymethyl) -8-methyl-2- (trifluoromethyl) -2H-pyrano [2,3-c] pyridine-3-carboxylic acid; 6- (trifluoromethyl) -6h-1,3-dioxolo [4,5-g] [1] benzopyran-7-carboxylic acid; And 3- (trifluoromethyl) -3H-benzofuro [3,2-f] [1] benzopyran-2-carboxylic acid. [6" claim-type="Currently amended] The compound of claim 2, wherein X is O; R is carboxyl; wherein R "is selected from hydrido and C 2 -C 6 -alkenyl; wherein R 1 is selected from C 1 -C 3 -perfluoroalkyl; wherein R 2 is Hydrido, halo, C 1 -C 6 -alkyl, phenyl-C 1 -C 6 -alkyl, phenyl-C 2 -C 6 -alkynyl, phenyl-C 2 -C 6 -alkenyl, C 1 -C 6 -alkoxy, phenyloxy, 5- or 6-membered heteroaryloxy, phenyl-C 1 -C 6 -alkyloxy, 5- or 6-membered heteroaryl-C 1 -C 6 -alkyloxy, C 1 -C 6 -haloalkyl, C 1 -C 6 -haloalkoxy, N- (C 1 -C 6 -alkyl) amino, N, N-di- (C 1 -C 6 -alkyl) amino, N-phenylamino, N -(Phenyl-C 1 -C 6 -alkyl) amino, N-heteroarylamino, N- (heteroaryl-C 1 -C 6 -alkyl) amino, nitro, amino, aminosulfonyl, N- (C 1- C 6 -alkyl) aminosulfonyl, N, N-di- (C 1 -C 6 -alkyl) aminosulfonyl, N-arylaminosulfonyl, N-heteroarylaminosulfonyl, N- (phenyl-C 1 -C 6 - alkyl) aminosulfonyl, N- (heteroaryl, -C 1 -C 6 - Al ) Aminosulfonyl, 5- to 8-membered heterocyclic ilsul sulfonyl, C 1 -C 6 - alkylsulfonyl, optionally substituted phenyl, optionally substituted 5-or 6-membered heteroaryl, phenyl -C 1 -C 6 substituted At least one radical independently selected from -alkylcarbonyl, heteroarylcarbonyl, phenylcarbonyl, aminocarbonyl, and C 1 -C 6 -alkylcarbonyl; A ring atoms A 1 , A 2 , A 3 And A 4 is an benzopyran derivative compound for the treatment of inflammation, wherein at least three of A 1 , A 2 , A 3 and A 4 are carbon and are selected from carbon and nitrogen or isomers or pharmacologically acceptable salts thereof. [7" claim-type="Currently amended] The compound of claim 6, wherein X is O; R is carboxyl; wherein R "is selected from hydrido and ethenyl; wherein R 1 is selected from trifluoromethyl and pentafluoroethyl; wherein R 2 is hydrido, chloro, bromo, Fluorine, iodo, methyl, t-butyl, ethenyl, ethynyl, 5-chloro-1-pentynyl, 1-pentynyl, 3,3-dimethyl-1-butynyl, benzyl, phenylethyl, phenyl-e Tinyl, 4-chlorophenyl-ethynyl, 4-methoxyphenyl-ethynyl, phenylethenyl, methoxy, methylthio, methylsulfinyl, phenyloxy, phenylthio, phenylsulfinyl, pyridyloxy, thienyloxy , Furyloxy, phenylmethoxy, methylenedioxy, benzyloxymethyl, trifluoromethyl, difluoromethyl, pentafluoroethyl, trifluoromethoxy, trifluoromethylthio, hydroxymethyl, hydroxy-trifluoroethyl, meth Methoxymethyl, hydroxyiminomethyl, N-methylamino, N-phenylamino, N- (benzyl) amino, nitro, Ano, amino, aminosulfonyl, N-methylaminosulfonyl, N-phenylaminosulfonyl, N-furylaminosulfonyl, N- (benzyl) aminosulfonyl, N- (furylmethyl) aminosulfonyl, benzylsul Phenyl, benzimidazolyl, thienyl substituted with one or more radicals selected from phenyl, phenylethylaminosulfonyl, furylsulfonyl, methylsulfonyl, phenyl, chloro, fluorine, bromo, methoxy, methylthio and methylsulfonyl , chloro, furyl, chloro, benzyl carbonyl, furyl carbonyl, phenyl-carbonyl, aminocarbonyl, formyl, and phenyl-carbonyl-cost one or more radicals independently selected from thienyl substituted with a; in the A ring atoms A 1 A benzopyran derivative compound for treating inflammation, which is a compound of formula (I ′) or an isomer or a pharmacologically acceptable salt thereof, wherein one of A, A 2 , A 3 , and A 4 is nitrogen and the other three are carbon. [8" claim-type="Currently amended] The compound of claim 1, wherein X is O; R is carboxyl; wherein R "is selected from hydrido and ethenyl; wherein R 1 is selected from trifluoromethyl and pentafluoroethyl; wherein R 2 is hydrido, chloro, bromo, Fluorine, iodo, methyl, t-butyl, ethenyl, ethynyl, 5-chloro-1-pentynyl, 1-pentynyl, 3,3-dimethyl-1-butynyl, benzyl, phenylethyl, phenyl-e Tinyl, 4-chlorophenyl-ethynyl, 4-methoxyphenyl-ethynyl, phenylethenyl, methoxy, methylthio, methylsulfinyl, phenyloxy, phenylthio, phenylsulfinyl, pyridyloxy, thienyloxy , Furyloxy, phenylmethoxy, methylenedioxy, benzyloxymethyl, trifluoromethyl, difluoromethyl, pentafluoroethyl, trifluoromethoxy, trifluoromethylthio, hydroxymethyl, hydroxy-trifluoroethyl, meth Methoxymethyl, hydroxyiminomethyl, N-methylamino, N-phenylamino, N- (benzyl) amino, nitro, Ano, amino, aminosulfonyl, N-methylaminosulfonyl, N-phenylaminosulfonyl, N-furylaminosulfonyl, N- (benzyl) aminosulfonyl, N- (furylmethyl) aminosulfonyl, benzylsul Phenyl, benzimidazolyl, thienyl substituted with one or more radicals selected from phenyl, phenylethylaminosulfonyl, furylsulfonyl, methylsulfonyl, phenyl, chloro, fluorine, bromo, methoxy, methylthio and methylsulfonyl , chloro, furyl, chloro, benzyl carbonyl, furyl carbonyl, phenyl-carbonyl, aminocarbonyl, formyl, and phenyl-carbonyl-cost one or more radicals independently selected from thienyl substituted with a; in the A ring atoms A 1 A benzopyran derivative compound for treating inflammation, which is a compound of formula (I ′) or an isomer or a pharmacologically acceptable salt thereof, wherein one of A, A 2 , A 3 , and A 4 is nitrogen and the other three are carbon. [9" claim-type="Currently amended] The compound of claim 7, wherein X is O; wherein R is carboxyl; wherein R ″ is selected from hydrido and ethenyl; wherein R 1 is selected from trifluoromethyl and pentafluoroethyl; Wherein R 2 is hydrido, chloro, bromo, fluorine, iodo, methyl, t-butyl, ethenyl, ethynyl, 5-chloro-1-pentynyl, 1-pentynyl, 3,3,- Dimethyl-1-butynyl, benzyl, phenylethyl, phenyl-ethynyl, 4-chlorophenyl-ethynyl, 4-methoxyphenyl-ethynyl, phenylethenyl, methoxy, methylthio, methylsulfinyl, phenyloxy , Phenylthio, phenylsulfinyl, pyridyloxy, thienyloxy, furyloxy, phenylmethoxy, methylenedioxy, benzyloxymethyl, trifluoromethyl, difluoromethyl, pentafluoroethyl, trifluoromethoxy, trifluor Methylthio, hydroxymethyl, hydroxy-trifluoroethyl, methoxymethyl, hydroxyaminomethyl, N-methylami , N-phenylamino, N- (benzyl) amino, nitro, cyano, amino, aminosulfonyl, N-methylaminosulfonyl, N-phenylaminosulfonyl, N-furylaminosulfonyl, N- (benzyl) Aminosulfonyl, N- (furylmethyl) aminosulfonyl, benzylsulfonyl, phenylethylaminosulfonyl, furylsulfonyl, methylsulfonyl, phenyl, chloro, fluorine, bromo, methoxy, methylthio and methylsulfonyl Thienyl substituted with phenyl, benzimidazolyl, thienyl, chloro, furyl, chloro, benzylcarbonyl, furylcarbonyl, phenylcarbonyl, aminocarbonyl, formyl, and methylcarbonyl substituted with one or more radicals selected from Benzopyran derivative compounds for the treatment of inflammation, which are compounds of formula (I ′) or isomers or pharmacologically acceptable salts thereof, wherein A ring atoms A 1 , A 2 , A 3 , and A 4 are carbon. [10" claim-type="Currently amended] The benzopyran derivative compound for treating inflammation according to claim 9, wherein the compound is selected from the following compounds and pharmacologically acceptable salts thereof; 6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-7-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-7- (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-7- (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (1-methylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7- (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-trifluoromethoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6-trifluoromethoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,7-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; (S) -6,8-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-dichloro-7-methoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-2-trifluoromethyl-2H-1-benzothiopyran-3-carboxylic acid; (S) -6-chloro-2-trifluoromethyl-2H-1-benzothiopyran-3-carboxylic acid; 6-cyano-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-cyano-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-hydroxymethyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (difluoromethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 2,6-bis (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 5,6,7-trichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6,7,8-trichloro-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (methylthio) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (pentafluoroethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 2- (trifluoromethyl) -6-[(trifluoromethyl) thio] -2H-1-benzothiopyran-3-carboxylic acid; 6,8-dichloro-7-methyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-benzoyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (4-chlorobenzoyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (4-hydroxybenzoyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-phenoxy-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 2- (trifluoromethyl) -6- [4- (trifluoromethyl) phenoxy) -2H-1-benzopyran-3-carboxylic acid; (S) -2- (trifluoromethyl) -6- [4- (trifluoromethyl) phenoxy) -2H-1-benzopyran-3-carboxylic acid; 6- (4-methoxyphenoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (3-chloro-4-methoxyphenoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (4-chlorophenoxy) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 8-chloro-2- (trifluoromethyl) -6- [4- (trifluoromethyl) phenoxy] -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-cyano-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (2-thienyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (phenylethynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-[(4-chlorophenyl) ethynyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-[(4-methoxyphenyl) ethynyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; (S) -6-chloro-8-[(4-methoxyphenyl) ethynyl] -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (phenylethynyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (4-chlorophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-phenyl-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6- (4-bromophenyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (4-methoxyphenyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6- (2,2,2-trifluoro-1-hydroxyethyl) -2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid; [11" claim-type="Currently amended] The compound of claim 2, wherein X is S; wherein R is carboxyl; wherein R 1 is selected from C 1 -C 3 -perfluoroalkyl; wherein R 2 is hydrido, halo, C 1 -C 6 -alkyl, phenyl-C 1 -C 6 -alkyl, phenyl-C 2 -C 6 -alkynyl, phenyl-C 2 -C 6 -alkenyl, C 1 -C 6 -alkoxy, phenyloxy, 5 Or 6-membered heteroaryloxy, phenyl-C 1 -C 6 -alkoxy, 5- or 6-membered heteroaryl-C 1 -C 6 -alkyloxy, C 1 -C 6 -haloalkyl, C 1 -C 6 -haloalkoxy, C 1 -C 6 -alkylamino, N-phenylamino, N- (phenyl-C 1 -C 6 -alkyl) amino, N-heteroarylamino, N- (heteroaryl) -C 1- C 6 -alkylamino, nitro, amino, aminosulfonyl, N-alkylaminosulfonyl, N-arylaminosulfonyl, N-heteroarylaminosulfonyl, N- (phenyl-C 1 -C 6 -alkyl) amino Sulfonyl, N- (heteroaryl-C 1 -C 6 -alkyl) aminosulfonyl, 5- to 8-membered heterocyclylsulfonyl, C 1 -C 6 -alkylsulfonyl, optionally substituted phenyl Independent from optionally substituted 5- or 6-membered heteroaryl, phenyl-C 1 -C 6 -alkylcarbonyl, heteroarylcarbonyl, phenylcarbonyl, aminocarbonyl, and C 1 -C 6 -alkylcarbonyl One or more radicals selected from the above; wherein the A ring atoms A 1 , A 2 , A 3 , and A 4 are oxygen and provided that at least three of A 1 , A 2 , A 3 , and A 4 are carbon; A benzothiopyran compound or isomer thereof or a pharmacologically acceptable salt thereof, independently selected from nitrogen, for treating benzopyran derivatives. [12" claim-type="Currently amended] The compound of claim 11, wherein X is S; wherein R is carboxyl; wherein R ″ is selected from hydrido and ethenyl; wherein R 1 is selected from trifluoromethyl and pentafluoroethyl; Wherein R 2 is hydrido, chloro, bromo, fluorine, iodo, methyl, t-butyl, ethenyl, ethynyl, 5-chloro-1-pentynyl, 1-pentynyl, 3,3-dimethyl -1-butynyl, benzyl, phenylethyl, phenyl-ethynyl, phenylethenyl, methoxy, methylthio, methylsulfinyl, phenyloxy, phenylthio, phenylsulfinyl, pyridyloxy, thienyloxy, furyloxy , Phenylmethoxy, methylenedioxy, benzyloxymethyl, trifluoromethyl, difluoromethyl, pentafluoroethyl, trifluoromethoxy, trifluoromethylthio, hydroxymethyl, hydroxy-trifluoroethyl, methoxymethyl, Hydroxyiminomethyl, N-methylamino, N-phenylamino, N- (benzyl) amino, nitro, c Furnace, amino, aminosulfonyl, N-methylaminosulfonyl, N-phenylaminosulfonyl, N-furylaminosulfonyl, N- (benzyl) aminosulfonyl, N- (furylmethyl) aminosulfonyl, benzylsul Phenyl, benzimidazolyl, thienyl substituted with one or more radicals selected from phenyl, phenyletherylaminosulfonyl, furylsulfonyl, methylsulfonyl, phenyl, chloro, fluorine, bromo, methoxy, methylthio and methylsulfonyl , chloro, furyl, chloro, benzyl carbonyl, furyl carbonyl, phenyl-carbonyl, aminocarbonyl, formyl, and methyl-carbonyl a independently are one or more radicals selected from thienyl substituted with; a ring atoms in the a 1 , A 2 , A 3 , and A 4 are carbon compounds of formula (I ′) or isomers thereof or pharmacologically acceptable salts thereof. [13" claim-type="Currently amended] 13. The benzopyran derivative compound for treating inflammation according to claim 12, wherein the compound is selected from the following compounds and their isomers or pharmacologically acceptable salts thereof; 6-chloro-2-trifluoromethyl-2H-1-benzothiopyran-3-carboxylic acid; 6-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 6,8-dimethyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 6- (1,1-dimethylethyl) -2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 7-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 6,7-dimethyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 8-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 6-chloro-7-methyl-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 7-chloro-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 6,7-dichloro-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid; 2- (trifluoromethyl) -6-[(trifluoromethyl) thio] -2H-1-benzothiopyran-3-carboxylic acid; 6,8-dichloro-2-trifluoromethyl-2H-1-benzothiopyran-3-carboxylic acid. [14" claim-type="Currently amended] 3. A compound according to claim 2, wherein X is NR a ; wherein R a is hydrido, C 1 -C 3 -alkyl, phenyl-C 1 -C 3 -alkyl, acyl and carboxy-C 1 -C 3- R is carboxyl; wherein R 1 is selected from C 1 -C 3 -perfluoroalkyl; wherein R 2 is hydrido, halo, C 1 -C 6 -alkyl, phenyl -C 1 -C 6 - alkyl, phenyl -C 2 -C 6 - alkynyl, phenyl, -C 2 -C 6 - alkenyl, C 1 -C 6 - alkoxy, phenyloxy, 5-or 6-membered heteroaryl Oxy, phenyl-C 1 -C 6 -alkyloxy, 5- or 6-membered heteroaryl-C 1 -C 6 -alkyloxy, C 1 -C 6 -haloalkyl, C 1 -C 6 -haloalkoxy, C 1- C 6 -alkylamino, N-phenylamino, N- (phenyl-C 1 -C 6 -alkyl) amino, N-heteroarylamino, N- (heteroaryl) -C 1 -C 6 -alkylamino, Nitro, amino, aminosulfonyl, N-alkylaminosulfonyl, N-arylaminosulfonyl, N-heteroarylaminosulfonyl, N- (phenyl-C 1 -C 6 -alkyl) aminosulfonyl, N- ( Hete Aryl -C 1 -C 6 - alkyl) aminosulfonyl, 5- to 8-membered heterocyclic ilsul sulfonyl, C 1 -C 6 - alkylsulfonyl, optionally substituted phenyl, optionally substituted 5-or 6-membered heteroaryl One or more radicals independently selected from aryl, phenyl-C 1 -C 6 -alkylcarbonyl, heteroarylcarbonyl, phenylcarbonyl, aminocarbonyl and C 1 -C 6 -alkylcarbonyl; A ring atoms A 1 , A 2 , A 3, and A 4 are dihydroquinoline compounds selected from carbon and nitrogen, provided that at least three of A 1 , A 2 , A 3, and A 4 are carbon; Benzopyran derivative compounds for the treatment of inflammation, which are isomers or pharmacologically acceptable salts thereof. [15" claim-type="Currently amended] 15. The compound of claim 14, wherein X is NR a ; wherein R a is hydrido, methyl, ethyl, (4-trifluoromethyl) benzyl, (4-chloromethyl) benzyl, (4-methoxy) benzyl , (4-cyano) benzyl, and (4-nitro) benzyl; wherein R is carboxyl; wherein R "is selected from hydrido, ethenyl; wherein R 1 is trifluoromethyl And pentafluoroethyl; wherein R 2 is hydrido, chloro, bromo, fluorine, iodo, methyl, t-butyl, ethenyl, ethynyl, 5-chloro-1-pentynyl, 1- Pentynyl, 3,3-dimethyl-1-butynyl, benzyl, phenylethyl, phenyl-ethynyl, 4-chlorophenyl-ethynyl, 4-methoxyphenyl-ethynyl, phenylethenyl, methoxy, methylthio , Methylsulfinyl, phenyloxy, phenylthio, phenylsulfinyl, pyridyloxy, thienyloxy, furyloxy, phenylmethoxy, methylenedioxy, benzyloxymethyl, trifluoromethyl, difluoromethyl, pentaflu Leethyl, trifluoromethoxy, trifluoromethylthio, hydroxymethyl, hydroxy-trifluoroethyl, methoxymethyl, hydroxyaminomethyl, N-methylamino, N-phenylamino, N- (benzyl) amino, Nitro, cyano, amino, aminosulfonyl, N-methylaminosulfonyl, N-phenylaminosulfonyl, N-furylaminosulfonyl, N- (benzyl) aminosulfonyl, N- (furylmethyl) aminosulfonyl , Phenyl, benzimidazolyl, thienyl, chloro, furyl, chloro, substituted with one or more radicals selected from furylsulfonyl, methylsulfonyl, phenyl, chloro, fluorine, bromo, methoxy, methylthio and methylsulfonyl At least one radical independently selected from benzylcarbonyl, furylcarbonyl, phenylcarbonyl, aminocarbonyl, formyl, and thienyl substituted with methylcarbonyl; A ring atoms A 1 , A 2 , A 3 , and A 4 is a compound or the formula I 'carbon of Consists acceptable salt thereof or a pharmacologically jilche. [16" claim-type="Currently amended] The benzopyran derivative compound for treating inflammation according to claim 15, wherein the compound is selected from the following compounds and their isomers or pharmacologically acceptable salts thereof; 6-chloro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6,8-dichloro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6,7-difluoro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-iodo-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-bromo-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 1,2-dihydro-6- (trifluoromethoxy) -2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6- (trifluoromethyl) -1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-cyano-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-chloro-1,2-dihydro-1-methyl-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-chloro-1,2-dihydro-2- (trifluoromethyl) -1-[[4- (trifluoromethyl) phenyl] methyl] -3-quinolinecarboxylic acid; 6-chloro-1-[(4-chlorophenyl) methyl] -1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-chloro-1,2-dihydro-2- (trifluoromethyl) -1-[[4- (methoxy) phenyl] methyl] -3-quinolinecarboxylic acid; 6-chloro-1-[(4-cyanophenyl) methyl] -1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-chloro-1,2-dihydro-1-[(4-nitrophenyl) methyl] -2- (trifluoromethyl) -3-quinolinecarboxylic acid; 6-chloro-1,2-dihydro-1-ethyl-2- (trifluoromethyl) -3-quinolinecarboxylic acid; (S) -6-chloro-1,2-dihydro-2- (trifluoromethyl) -3-quinolinecarboxylic acid. [17" claim-type="Currently amended] The compound of claim 2, wherein X is selected from O, S, and NR a ; wherein R a is hydrido, C 1 -C 3 -alkyl, phenyl-C 1 -C 3 -alkyl, acyl and Carboxy-C 1 -C 3 -alkyl; wherein R is carboxyl; wherein R 1 is selected from C 1 -C 3 -perfluoroalkyl; Wherein the A ring atoms A 1 , A 2 , A 3 and A 4 are selected from carbon and nitrogen provided that at least three of A 1 , A 2 , A 3 and A 4 are carbon; 2 is a benzopyran derivative compound for treating inflammation, which is a compound or an isomer thereof or a pharmacologically acceptable salt thereof forming a naphthyl or quinolyl radical together with ring A. [18" claim-type="Currently amended] The compound of claim 17, wherein X is selected from O, S, and NR a ; wherein R a is hydrido, methyl, ethyl, (4-trifluoromethyl) benzyl, (4-chloromethyl) benzyl , (4-methoxy) benzyl, (4-cyano) benzyl, and (4-nitro) benzyl; wherein R is carboxyl; Wherein R ″ is selected from hydrido and ethenyl; wherein R 1 is selected from trifluoromethyl and pentafluoroethyl; wherein the A ring atoms A 1 , A 2 , A 3 , and A 4 are carbon Wherein R 2 is a compound of formula (I ′) or an isomer thereof or a pharmacologically acceptable salt thereof that forms naphthyl, or quinolyl radical, together with ring A; [19" claim-type="Currently amended] 19. The benzopyran derivative compound for treating inflammation according to claim 18, wherein the compound is selected from the following compounds and their isomers or pharmacologically acceptable salts thereof; 2-trifluoromethyl-2H-naphtho [1,2-b] pyran-3-carboxylic acid; 2-trifluoromethyl-3H-naphtho [2,1-b] pyran-3-carboxylic acid; 2-trifluoromethyl-2H-naphtho [2,3-b] pyran-3-carboxylic acid; 5- (hydroxymethyl) -8-methyl-2- (trifluoromethyl) -2H-pyrano [2,3-c] pyridine-3-carboxylic acid; 6- (trifluoromethyl) -6h-1,3-dioxolo [4,5-g] [1] benzopyran-7-carboxylic acid; and 3- (trifluoromethyl) -3H-benzofuro [3,2-f] [1] benzopyran-2-carboxylic acid. [20" claim-type="Currently amended] Benzopyran derivative compounds for the treatment of inflammation, which are Formula I and its isomers or pharmacologically acceptable salts thereof; Wherein X is selected from O or S or NR a ; Wherein R a is alkyl; Wherein R is selected from carboxyl, aminocarbonyl, alkylsulfonylaminocarbonyl and alkoxycarbonyl; Wherein R 1 is selected from haloalkyl, alkyl, arylalkyl, cycloalkyl and aryl optionally substituted with one or more radicals selected from alkylthio, nitro and alkylsulfonyl; Wherein R 2 is hydrido, halo, alkyl, aralkyl, alkoxy, aryloxy, heteroaryloxy, arylalkyloxy, heteroaralkyloxy, haloalkyl, haloalkoxy, alkylamino, arylamino, aralkylamino, Heteroarylamino, heteroarylalkylamino, nitro, amino, aminosulfonyl, alkylaminosulfonyl, arylaminosulfonyl, heteroarylaminosulfonyl, arylalkylaminosulfonyl, heteroaralkylaminosulfonyl, heterocyclosulfonyl At least one radical selected from alkylsulfonyl, optionally substituted aryl, optionally substituted heteroaryl, aralkylcarbonyl, heteroarylcarbonyl, arylcarbonyl, aminocarbonyl, and alkylcarbonyl; Or wherein R 2 together with Ring A form a naphthyl radical. [21" claim-type="Currently amended] 21. The method of claim 20, wherein X is oxygen or sulfur; Wherein R is selected from carboxyl, lower alkyl, lower aralkyl and lower alkoxycarbonyl; Wherein R 1 is selected from lower haloalkyl, lower cycloalkyl and phenyl; wherein R 2 is hydrido, halo, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, lower alkylamino, nitro, amino , Aminosulfonyl, lower alkylaminosulfonyl, 5- or 6-membered heteroarylalkylaminosulfonyl, lower aralkylaminosulfonyl, 5- or 6-membered nitrogen containing heterocyclosulfonyl, lower alkylsulfonyl, optionally At least one radical selected from substituted phenyl, lower aralkylcarbonyl, and lower alkylcarbonyl; wherein R 2 is a compound of formula I or an isomer or pharmacologically acceptable thereof that forms a naphthyl radical with ring A; Benzopyran derivative compounds for treating inflammation as salts. [22" claim-type="Currently amended] The compound of claim 21, wherein X is oxygen or sulfur; wherein R is carboxyl; wherein R 1 is selected from lower haloalkyl; wherein R 2 is hydrido, halo, lower alkyl, lower haloalkyl Lower haloalkoxy, lower alkylamino, amino, aminosulfonyl, lower alkylaminosulfonyl, 5- or 6-membered heteroarylalkylaminosulfonyl, lower aralkylaminosulfonyl, lower alkylsulfonyl, 6-membered nitrogen A benzopyran derivative compound for the treatment of inflammation, which is a compound of formula (I) or an isomer or a pharmacologically acceptable salt thereof, which is at least one radical selected from containing heterocyclosulfonyl, optionally substituted phenyl, lower aralkylcarbonyl, and lower alkylcarbonyl. [23" claim-type="Currently amended] The compound of claim 22, wherein R is carboxyl; wherein R 1 is fluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluoroethyl, difluoromethyl, and trifluorine. Wherein R 2 is hydrido, chloro, fluorine, bromo, iodo, methyl, ethyl, isopropyl, t-butyl, butyl, isobutyl, pentyl, hexyl, methoxy, ethoxy, isopropyloxy Tertbutyloxy, trifluoromethyl, difluoromethyl, trifluoromethoxy, amino, N, N-dimethylamino, N, N-diethylamino, N-phenylmethylaminosulfonyl, N-phenylethylaminosulfonyl , N- (2-furylmethyl) aminosulfonyl, nitro, N, N-dimethylaminosulfonyl, aminosulfonyl, N-methylaminosulfonyl, N-ethylsulfonyl, 2,2-dimethylethylaminosulfonyl , N, N-dimethylaminosulfonyl, N- (2-methylpropyl) aminosulfonyl, N-morpholinosul Carbonyl, methyl sulfonyl, carbonyl benzyl, 2,2-dimethylpropyl-carbonyl, phenylacetyl, and is one or more radicals selected from phenyl; R 2 is a benzopyran derivative compound for the treatment of inflammation which is a compound of formula (I) or an isomer or a pharmacologically acceptable salt thereof which forms together with ring A a naphthyl radical. [24" claim-type="Currently amended] The method of claim 23, wherein R is carboxyl; wherein R 1 is trifluoromethyl or pentafluoroethyl; And wherein R2 is hydrido, chloro, fluorine, bromo, iodo, methyl, ethyl, isopropyl, t-butyl, methoxy, trifluoromethyl, trifluoromethoxy, N-phenylmethylaminosulfonyl, N-phenylethylaminosulfonyl, N-methylaminosulfonyl, N- (2,2-dimethylethyl) aminosulfonyl, dimethylaminosulfonyl, 2-methylpropylaminosulfonyl, N-morpholinosulfonyl, methyl Sulfonyl, benzylcarbonyl, and phenyl; R 2 is a benzopyran derivative compound for the treatment of inflammation, which is a compound of formula (I) or an isomer or a pharmacologically acceptable salt thereof which forms together with ring A a naphthyl radical. [25" claim-type="Currently amended] The benzopyran derivative compound for treating inflammation according to claim 24, wherein the compound is selected from the following compounds and their isomers or pharmacologically acceptable salts thereof; 6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-7-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8- (1-methylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-7- (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-8- (1-methylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7- (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-bromo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-trifluoromethoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 5,7-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-phenyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7,8-dimethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-bis (1,1-dimethylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7- (1-methylethyl) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7-phenyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-7-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-7-phenyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,7-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 2-trifluoromethyl-3H-naphtho [2,1-b] pyran-3-carboxylic acid; 6-chloro-8-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-chloro-6-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-chloro-6-methoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-bromo-8-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-bromo-6-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-bromo-6-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-bromo-5-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-chloro-8-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-bromo-8-methoxy-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[[(phenylmethyl) amino] sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[(dimethylamino) sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6- (methylamino) sulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[(4-morpholino) sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[(1,1-dimethylethyl) aminosulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[(2-methylpropyl) aminosulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-methylsulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-chloro-6-[[(phenylmethyl) amino] sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-phenylacetyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-dibromo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 8-chloro-5,6-dimethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6,8-dichloro- (S) -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-benzylsulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[[N- (2-furylmethyl) amino] sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-[[N- (2-phenylethyl) amino] sulfonyl] -2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 6-iodo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; 7- (1,1-dimethylethyl) -2-pentafluoroethyl-2H-1-benzopyran-3-carboxylic acid; and 6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid. [26" claim-type="Currently amended] Benzopyran derivative compounds for the treatment of inflammation of compounds of formula (II) or isomers thereof or pharmacologically acceptable salts thereof; Wherein X is selected from O, S, and NR a ; R 2 is lower haloalkyl; Wherein R 3 is selected from hydrido, and halo; Wherein R 4 is hydrido, halo, lower alkyl, lower haloalkoxy, lower alkoxy, lower aralkylcarbonyl, lower dialkylaminosulfonyl, lower alkylaminosulfonyl, lower aralkylaminosulfonyl, lower heteroar Alkylaminosulfonyl, and nitrogen-containing heterocyclosulfonyl that is 5- or 6-membered; Wherein R 5 is selected from hydrido, lower alkyl, halo, lower alkoxy, and aryl; And Wherein R 6 is selected from hydrido, halo, lower alkyl, lower alkoxy, and aryl. [27" claim-type="Currently amended] Benzopyran derivative compounds for treating inflammation, which are compounds of Formula (IIa) or isomers thereof or pharmacologically acceptable salts thereof; Wherein R 3 is selected from hydrido, lower alkyl, lower hydrooxyalkyl, lower alkoxy and haloboter; Wherein R 4 is hydrido, halo, lower alkyl, lower alkylthio, lower haloalkyl, amino, aminosulfonyl, lower alkylsulfonyl, lower alkylsulfinyl, lower alkoxyalkyl, lower alkylcarbonyl, formyl, cya Furnace, lower haloalkylthio, substituted or unsubstituted phenylcarbonyl, lower haloalkoxy, lower alkoxy, lower aralkylcarbonyl, lower dialkylaminosulfonyl, lower alkylaminosulfonyl, lower aralkylaminosulfonyl, lower Heteroaralkylaminosulfonyl, 5- or 6-membered heteroaryl, lower hydrooxyalkyl, optionally substituted phenyl and nitrogen-containing heterocyclosulfonyl that is 5- or 6-membered; Wherein R 5 is selected from hydrido, lower alkyl, halo, lower haloalkyl, lower alkoxy, and phenyl; And Wherein R 6 is selected from hydrido, halo, cyano, hydrooxyiminomethyl, lower hydroxyalkyl, lower alkynyl, phenylalkynyl, lower alkyl, lower alkoxy, formyl and phenyl. [28" claim-type="Currently amended] The compound of claim 27, wherein R 3 is selected from hydrido and chloro; Wherein R 4 is chloro, methyl, t-butyl, methylthio, trifluoromethyl, difluoromethyl, pentafluoromethyl, trifluoromethylsulfide, trifluoromethooxy, cyano, substituted or unsubstituted phenylcarbonyl , And substituted or unsubstituted phenyl; Wherein R 5 is selected from hydrido, methyl, t-butyl, chloro; and wherein R 6 is hydrido, chloro, thienyl, hydroxyiminomethyl, substituted or unsubstituted phenylethynyl, and A benzopyran derivative compound for treating inflammation, which is a compound of formula IIa or an isomer thereof or a pharmacologically acceptable salt thereof, which is substituted or unsubstituted phenyl. [29" claim-type="Currently amended] Benzopyran derivative compounds for treating inflammation, which are compounds of Formula (IIb) or isomers thereof or pharmacologically acceptable salts thereof; Wherein R 3 is selected from hydrido, lower alkyl, lower hydroxyalkyl, lower alkoxy and halo; Wherein R 4 is hydrido, halo, lower alkyl, lower alkylthio, lower haloalkyl, amino, aminosulfonyl, lower alkylsulfonyl, lower alkylsulfinyl, lower alkoxyalkyl, lower alkylcarbonyl, formyl, cya Furnace, lower haloalkylthio, substituted or unsubstituted phenylcarbonyl, lower haloalkoxy, lower alkoxy, lower aralkylcarbonyl, lower dialkylaminosulfonyl, lower alkylaminosulfonyl, lower aralkylaminosulfonyl, Lower heteroaralkylaminosulfonyl, 5- or 6-membered heteroaryl, lower hydrooxyalkyl, optionally substituted phenyl and nitrogen-containing heterocyclosulfonyl that is 5- or 6-membered; Wherein R 5 is selected from hydrido, lower alkyl, halo, lower haloalkyl, lower alkoxy, and phenyl; And Wherein R 6 is selected from hydrido, halo, cyano, hydrooxyiminomethyl, lower hydroxyalkyl, lower alkynyl, phenylalkynyl, lower alkyl, lower alkoxy, formyl and phenyl. [30" claim-type="Currently amended] The compound of claim 29, wherein R 3 is selected from hydrido and chloro; wherein R 4 is chloro, methyl, t-butyl, methylthio, trifluoromethyl, difluoromethyl, pentafluoromethyl, trifluoro Methylsulfide, trifluoromethoxy, cyano, substituted or unsubstituted phenylcarbonyl, and substituted or unsubstituted phenyl; Wherein R 5 is selected from hydrido, methyl, t-butyl, chloro; and wherein R 6 is hydrido, chloro, thienyl, hydroxyiminomethyl, substituted or unsubstituted phenylethynyl, and A benzopyran derivative compound for treating inflammation, which is a compound of formula (IIb) or an isomer thereof or a pharmacologically acceptable salt thereof, which is substituted or unsubstituted phenyl. [31" claim-type="Currently amended] Benzopyran derivative compounds for treating inflammation, which are compounds of Formula (IIc) or isomers thereof or pharmacologically acceptable salts thereof; Wherein R a is selected from hydrido and lower aralkyl; Wherein R 3 is selected from hydrido, lower alkyl, lower hydroxyalkyl, lower alkoxy and halo; Wherein R 4 is hydrido, halo, lower alkyl, lower alkylthio, lower haloalkyl, amino, aminosulfonyl, lower alkylsulfonyl, lower alkylsulfinyl, lower alkoxyalkyl, lower alkylcarbonyl, formyl, cya Furnace, lower haloalkylthio, substituted or unsubstituted phenylcarbonyl, lower haloalkoxy, lower alkoxy, lower aralkylcarbonyl, lower dialkylaminosulfonyl, lower alkylaminosulfonyl, lower aralkylaminosulfonyl, Lower heteroaralkylaminosulfonyl, 5- or 6-membered heteroaryl, lower hydrooxyalkyl, optionally substituted phenyl and 5- or 6-membered nitrogen containing heterocyclosulfonyl; Wherein R 5 is selected from hydrido, lower alkyl, halo, lower haloalkyl, lower alkoxy, and phenyl; and Wherein R 6 is selected from hydrido, halo, cyano, hydrooxyiminomethyl, lower hydroxyalkyl, lower alkynyl, phenylalkynyl, lower alkyl, lower alkoxy, formyl and phenyl. [32" claim-type="Currently amended] The compound of claim 31, wherein R 3 is selected from hydrido and chloro; wherein R 4 is chloro, methyl, t-butyl, methylthio, trifluoromethyl, difluoromethyl, pentafluoromethyl, trifluoro Methyl sulfide, trifluoromethoxy, cyano, substituted or unsubstituted phenylcarbonyl, and substituted or unsubstituted phenyl; wherein R 5 is selected from hydrido, methyl, t-butyl, chloro ; And wherein R 6 is hydrido, chloro, thienyl, hydroxyiminomethyl, substituted or unsubstituted phenylethynyl, and substituted or unsubstituted phenyl, or an isomer or pharmacologically acceptable thereof. A salt thereof is a benzopyran derivative compound for treating inflammation. [33" claim-type="Currently amended] Cyclooxygenase-2 in a subject characterized by treating a subject with or prone to cyclooxygenase-2 mediated disease in an amount effective to treat the compound of claims 1-31 or a pharmacologically acceptable salt thereof. How to treat a mediated disease. [34" claim-type="Currently amended] The method of claim 33, wherein said cyclooxygenase-2 mediated disease is inflammation. [35" claim-type="Currently amended] The method of claim 33, wherein said cyclooxygenase-2 mediated disease is arteritis. [36" claim-type="Currently amended] The method of claim 33, wherein said cyclooxygenase-2 mediated disease is pain. [37" claim-type="Currently amended] 34. The method of claim 33, wherein said cyclooxygenase-2 mediated disease is fever. [38" claim-type="Currently amended] A pharmacological composition comprising a therapeutically effective amount of a compound, characterized in that the compound is selected from the class of compounds of claims 1-31 or pharmacologically acceptable salts thereof.
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同族专利:
公开号 | 公开日 CN1196692C|2005-04-13| IS5218A|1999-10-15| SK285931B6|2007-11-02| PL336414A1|2000-06-19| EA004499B1|2004-04-29| EP0977748A1|2000-02-09| IL132296D0|2001-03-19| BR9808953A|2000-08-01| SK138699A3|2000-10-09| OA11302A|2003-08-21| SI0977748T1|2003-10-31| EE9900506A|2000-06-15| CU23094A3|2005-10-19| JP2002511062A|2002-04-09| AP1149A|2003-03-10| US7109211B2|2006-09-19| BG103870A|2000-07-31| ID24320A|2000-07-13| CA2287214C|2009-12-29| BG63820B1|2003-02-28| ES2194314T3|2003-11-16| AU7125698A|1998-11-13| CN1515566A|2004-07-28| EP0977748B1|2003-03-26| AP9901677A0|1999-12-31| GEP20022739B|2002-04-10| EE04190B1|2003-12-15| DK977748T3| CA2287214A1|1998-10-29| EA199900853A1|2000-10-30| CN1257489A|2000-06-21| JP4577534B2|2010-11-10| NO995113L|1999-12-21| IS1976B|2005-01-14| AT235481T|2003-04-15| NO995113D0|1999-10-20| AR015372A1|2001-05-02| PT977748E|2003-07-31| DK0977748T3|2003-07-21| RS49763B|2008-04-04| HU0001352A2|2002-01-28| UA64746C2|2000-08-15| HK1025325A1|2003-08-22| NO325249B1|2008-03-10| US6034256A|2000-03-07| TR199902626T2|2000-06-21| WO1998047890A1|1998-10-29| DE69812603D1|2003-04-30| HU0001352A3|2002-12-28| AU742033B2|2001-12-13| KR100538258B1|2006-01-12| IL132296A|2006-08-20| US20050049252A1|2005-03-03| US6806288B1|2004-10-19| ZA9803287B|1999-04-20| DE69812603T2|2003-12-04| NZ500387A|2001-02-23|
引用文献:
公开号 | 申请日 | 公开日 | 申请人 | 专利标题
法律状态:
1997-04-21|Priority to US4448597P 1997-04-21|Priority to US60/044,485 1998-04-18|Application filed by 쥐.디. 씨얼리 앤드 컴퍼니 1998-04-18|Priority to PCT/US1998/007677 2001-03-15|Publication of KR20010020152A 2006-01-12|Application granted 2006-01-12|Publication of KR100538258B1
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申请号 | 申请日 | 专利标题 US4448597P| true| 1997-04-21|1997-04-21| US60/044,485|1997-04-21| PCT/US1998/007677|WO1998047890A1|1997-04-21|1998-04-18|Substituted benzopyran derivatives for the treatment of inflammation| 相关专利
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Structure for Equipping Band in a Plane Cathode Ray Tube
Process for preparation of 7 alpha-carboxyl 9, 11-epoxy steroids and intermediates useful therein an
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