PESTICIDAL COMPOSITIONS AND PEST CONTROL PROCESS

专利摘要:
pesticidal compositions and related processes. this document describes molecules that have the following formula ('' formula one '') formula one the molecules described in this document are related to the process field for producing molecules that are useful as pesticides (for example, acaricides, insecticides, molluscicides, and nematicides) ), such molecules, and processes for using such molecules to control pests.
公开号:BR112014000688B1
申请号:R112014000688-1
申请日:2012-07-11
公开日:2020-08-18
发明作者:Gary D. Crouse；David A. Demeter；Thomas C. Sparks；Nick X. Wang；William Hunter Dent；Carl Deamicis；Noormohamed M. Niyaz；Erich W. Baum；Lindsey Gayle Fischer；Natalie Christine Giampietro
申请人:Dow Agrosciences Llc；
IPC主号:

专利说明:

CROSS REFERENCES TO RELATED ORDERS
[001] This order claims priority for provisional order US 61 / 506,743, filed on July 12, 2011. The full content of this provisional order is incorporated here by reference in this order. FIELD OF THE INVENTION
[002] The molecules described in this document are related to the field of processes to produce molecules that are useful as pesticides (for example, acaricides, insecticides, molluscicides, and nematocides), such molecules, and processes of using such molecules to control pests. BACKGROUND OF THE INVENTION
[003] Pests cause millions of human deaths worldwide each year. In addition, there are more than ten thousand species of pests that cause losses in agriculture. World agriculture loses billions of US dollars each year.
[004] Termites cause damage to all types of private and public structures. Termite damage worldwide amounts to billions of US dollars each year.
[005] Stored food pests consume and adulterate stored food. Food stored around the world loses billions of dollars each year, but more importantly, deprives people of the necessary food.
[006] There is an acute need for new pesticides. Certain pests are developing resistance to pesticides in current use. Hundreds of pest species are resistant to one or more pesticides. The development of resistance to some of the older pesticides, such as DDT, carbamates, and organophosphates, is well known. However, resistance has been developed to some newer pesticides.
[007] Therefore, for many reasons, including the reasons above, a need exists for new pesticides. DEFINITIONS
[008] The examples provided in the definitions are generally not exhaustive and should not be construed as limiting the molecules described in this document. It is understood that a substituent must comply with the rules of chemical bonding and steric compatibility restrictions in relation to the particular molecule to which it is attached.
[009] "Alkenyl" means an acyclic, unsaturated (at least one carbon-carbon double bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, vinyl, ally, butenyl, pentenyl, and hexenyl.
[0010] "Alkenyloxy" means an alkenyl also consisting of a single carbon-oxygen bond, for example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy.
[0011] "Aloxy" means an alkyl also consisting of a single carbon-oxygen bond, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, and tert-butoxy.
[0012] "Alkyl" means an acyclic, saturated, branched or unbranched substituent consisting of carbon and hydrogen, for example, methyl, ethyl, propyl, isopropyl, butyl, and tert-butyl.
[0013] "Alquinyl" means an acyclic substituent, unsaturated (at least one carbon-carbon triple bond), branched or unbranched consisting of carbon and hydrogen, for example, ethynyl, propargyl, butynyl, and pentinyl.
[0014] "Alquinyloxy" means an alkynyl also consisting of a single carbon-oxygen bond, for example, pentynyloxy, hexynyloxy, heptinyloxy, and octinyloxy.
[0015] "Aryl" means a cyclic, aromatic substituent consisting of hydrogen and carbon, for example, phenyl, naphthyl, and biphenyl.
[0016] "Cycloalkenyl" means a monocyclic or polycyclic substituent, unsaturated (at least one carbon-carbon double bond) consisting of carbon and hydrogen, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl, norbornenyl, bicycle [2,2,2 ] octenyl, tetrahydronaphthyl, hexahydronaphthyl, and octahydronaphthyl.
[0017] "Cycloalkenyloxy" means a cycloalkenyl also consisting of a single carbon-oxygen bond, for example, cyclobutenyloxy, cyclopentenyloxy, norbornenyloxy, and bicyclo [2,2,2] octenyloxy.
[0018] "Cycloalkyl" means a monocyclic or polycyclic substituent, saturated consisting of carbon and hydrogen, for example, cyclopropyl, cyclobutyl, cyclopentyl, norbornila, bicyclo [2,2,2] octyl, and decahydronaphthyl.
[0019] "Cycloalkoxy" means a cycloalkyl also consisting of a single carbon-oxygen bond, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, norbornyloxy, and bicyclo [2,2,2] octyloxy.
[0020] "Halo" means fluorine, chlorine, bromine, and iodine.
[0021] "Haloalkoxy" means an alkoxy also consisting of one to the maximum possible number of identical or different halos, for example, fluoromethoxy, trifluoromethoxy, 2,2-difluoropropoxy, chloromethoxy, trichloromethoxy, 1,1,2,2-tetrafluoroethoxy , and pentafluoroethoxy.
[0022] "Haloalkyl" means an alkyl also consisting of, from one to the maximum possible number of identical or different halos, for example, fluoromethyl, trifluoromethyl, 2,2-difluoropropyl, chloromethyl, trichloromethyl, and 1,1,2 , 2-tetrafluoroethyl.
[0023] "Heterocyclyl" means a cyclic substituent that can be completely saturated, partially unsaturated or completely unsaturated, where the cyclic structure contains at least one carbon and at least one heteroatom, where said heteroatom is nitrogen, sulfur, or oxygen . Examples of aromatic heterocyclyl include, but are not limited to, benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl, cinolinyl, furanyl, indazolyl, indolyl, imidazolyl, isoindolyl, isoquinolinyl, oxyzazole, isoxinazole, isoxinazole, isoxinazole, isoxinazole, isoxinazole, isoxinol, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl, and triazolyl. Examples of fully saturated heterocyclics include, but are not limited to, piperazinyl, piperidine, morpholinyl, pyrrolidinyl, tetrahydrofuranyl, and tetrahydropyranyl. Examples of partially unsaturated heterocyclyl include, but are not limited to, 1,2,3,4-tetrahydro-quinolinyl, 4,5-dihydro-oxazolyl, 4,5-dihydro-1H-pyrazolyl, 4 , 5-dihydro-isoxazolyl, and 2,3-dihydro- [1,3,4] -oxadiazolyl. DETAILED DESCRIPTION OF THE INVENTION
[0024] This document describes molecules having the following formula (“Formula One”)
Formula One where:
[0025] Ar1 is selected from
[0026] furanyl, phenyl, pyridazinyl, pyridyl, pyrimidinyl, thienyl, or
[0027] (2) substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, or substituted thienyl, wherein said substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, and substituted thienil or more substituents independently selected from H, F, Cl, Br, I, CN, NO2, CI-CΘalkyl, CI-CΘhaloalkyl, C3-C6 cycloalkyl, C3-Ce halocycloalkyl, C3-Cβ cycloalkoxy, Cs-Ce halocclo- alkoxy, Ci-Cβ alkoxy, C, -C6 haloalkoxy, C2-C6 alkenyl, CrCealquinyl S (= OMCi-Cβ alkyl), S (= O) n (C, -C6 haloalkyl), OSO2 (CrC6alkyl), OSO2 (Ci- Cβ haloalkyl), C (= 0) NRW, (Ci-Cβ alkyl) NRW, C (= O) (Cr Cβ alkyl), C (= O) O (Ci-Cβ alkyl), C (= O) (Ci -Cβ haloalkyl), C (= O) O (C1-C6 haloalkyl), C (= O) (C3-C6 cycloalkyl), C (= O) O (C3-C6 cycloalkyl), C (= O) (C ^ C6 alkenyl), Clr & MCrCealkenyl), (C, -C6 alkyl) O (C1-C3alkyl), (C1-C6 alkyl) S (C1-Cs alkyl), C (-O) (Ci Ce al quil) C ( = O) O (Ci-Cθ alc ila), phenyl, phenoxy, substituted phenyl, and substituted phenoxy,
[0028] wherein such substituted phenyl and substituted phenoxy have one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2, C1-C6 alkyl, Ci-Ce haloalkyl, C3-C6 cycloalkyl, C3- C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, C-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyl, C2-C6 alkynyl, S (= O) n (Ci-Ce alkyl), S (= O ) n (Ci-Cθ haloalkyl), OSO2 (Ci-Ce alkyl), OSO2 (Ci-Ce halo-alkyl), C (= O) NRxRy, (Ci-C6 alkyl) NRxRy, C (= O) (Ci- C6 = alkyl), C (= O) O (C1-C6alkyl), C (= O) (C1-C6 haloalkyl), C (= O) O (C1-C6 haloalkyl), C (= O) (C3-C6 cycloalkyl) ), C (= O) O (C3-CΘ cycloalkyl), C (= O) (C2-C6 alkenyl), C (= O) O (C2-C6 alkenyl), (C-C6 alkyl) O (Ci- C6alkyl), (C1-6 alkyl) S (C1-6 alkyl), C (= O) (C1-6 alkyl) C (= O) O (C1-6 alkyl) phenyl, and phenoxy;
[0029] (B) Het is a 5- or 6-membered saturated or unsaturated heterocyclic ring that contains one or more heteroatoms independently selected from nitrogen, sulfur, or oxygen, and where Ar1 and Ar2 are not ortho to each other ( however they can be meta or for, such as for a five-membered ring they are 1.3 and for a 6-membered ring they are either 1.3 or 1.4), and where said heterocyclic ring can also be replaced by one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2, oxo, Ci-Cβ alkyl C1-Cβ haloalkyl, C3-Ce cycloalkyl, C3-C6 halocycloalkyl, C3-Cβ cycloalkoxy, C3-C6 halocycloalkoxy, CC. alkoxy, C.-C6 haloalkoxy, OC6 alkenyl, C2-C6 alkynyl, S (= O) „(C, -Cβalkyl), S (= O)„ (C, -C6 haloalkyl), OSθ2 (CrC6alkyl), OSO2 ( C, -C6 haloalkyl), C (= O) NRW, (Ci-Cβ alkyl) NRW, C (= O) (C, -Cβ alkyl), C (= O) O (C, -C6alkyl), C ( = O) (C1-C6 haloalkyl), C (= O) O (C, -C6 haloalkyl), C (= O) (C3-C6 cycloalkyl), C (= O) O (C3-C6 cycloalkyl), C (= O) (Cj-Cβ alkenyl), C (= O) O (C2-CB alkenyl), (Ci-Cβ alkyl) O (Ci-Cβ alkyl), (C1-C5 al quil) S (Ci-Ce alkyl), C (= O) (Ci-Ce alkyl) C (= O) O (Ci-C6alkyl), femla, phenoxy, substituted phenyl and substituted phenoxy,
[0030] wherein such substituted phenyl and substituted phenoxy have one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2, C1-C6 alkyl, Ci-Cβ haloalkyl, C3-C6 cycloalkyl, C3- C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, C-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyl, C2-C6 alkynyl, S (= O) n (Ci-C6 alkyl), S (= O) n (Ci-Ce haloalkyl), OSO2 (Ci-Ce alkyl), OSO2 (Ci-Ce halo-alkyl), C (= O) H, C (= O) NRxRy, (Ci-C6 alkyl) NRxRy, C ( = O) (C1-C6alkyl), C (= O) O (C1-C6alkyl), C (= O) (C1-C haloalkyl), C (= O) O (C1-C6 haloalkyl), C (= O ) (C3-C6 cycloalkyl), C (= O) O (C3-C6cycloalkyl), C (= O) (C2-C6 alkenyl), C (= O) O (C2-C6 alkenyl), (Ci-C6 alkyl ) O (C1-6 alkyl), (C1-6 alkyl) S (C1-6 alkyl), phenyl, and phenoxy;
[0031] (C) Ar2 is selected from
[0032] furanyl, phenyl, pyridazinyl, pyridyl, pyrimidinyl, thienyl, or
[0033] (2) substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, or substituted thienyl, wherein said substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, and substituted thienil, have one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2, CI-CΘalkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocyclo- alkoxy, Ci-Ce alkoxy, C, -C and haloalkoxy, Cz-Cβ alkenyl, C2-Cβ alkynyl, S (= O) „(C1-Cealkyl), S (= O)„ (Ci-C6 haloalkyl), OSO ^ CrCs alkyl), OSO2 (C1-C6 haloalkyl), C (= 0) NRW, (C1-C alkyl) NRW, C (= O) (Cf-C6 alkyl), C (= O) O (C1-C6 alkyl) ), C (= O) (C1-C6 haloalkyl), C (= O) O (C1-C haloalkyl), C (= O) (C3-C6 cycloalkyl), C (= O) O (C3-C6 cycloalkyl) ), C (= O) (C2-C6 alkenyl), C (= O) O (C2-C6 alkenyl), (C <-C6 alkyl) O (C1-C3 alkyl), (C, -C6 alkyl) S ( C 1 -C 6 alkyl), C (= O) (C, -C and alkyl) C (= O ) O (C1 -C6 alkyl), phenyl, phenoxy, substituted phenyl and substituted phenoxy,
[0034] wherein such substituted phenyl and substituted phenoxy have one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C6 cycloalkyl, C3- C6 halocycloalkyl, C3-C6cycloalkoxy, C3-C6halocycloalkoxy, C-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyl, C2-C6 alkynyl, S (= O) n (Ci-C6 alkyl), S (= O) n (Ci-Ce haloalkyl), OSO2 (Ci-Ce alkyl), OSO2 (Ci-Ce halo-alkyl), C (= O) H, C (= O) NRxRy '(Ci-C6 alkyl) NRxRy, C (= O) (C1-C6 alkyl), C (= O) O (C1-C alkyl), C (= O) (C1-C haloalkyl), C (= O) O (CI-CΘ haloalkyl), C (= O) (C3-C6 cycloalkyl), C (= O) O (C3-C6 cycloalkyl), C (= O) (Ci-Ce haloalkyl), C (= O) (C2-Ce alkenyl), C (= O ) O (C2-Ce alkenyl), (C1-C6 alkyl) O (C1-C6 alkyl), (C1-C6 alkyl) S (C1-C6 alkyl), C (= O) (C1-C6 alkyl) C ( = O) O (Ci-Ce alkyl), phenyl, and phenoxy);
[0035] (D) R1 is selected from H, CI-CΘalkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, S (= O) n (Ci-Ce alkyl), C (= O) NRxRy , (C1-C6 alkyl) NRxRy, C (= O) O (C1-C6 alkyl), C (= O) (C3-C6 cycloalkyl), C (= O) O (C3-C cycloalkyl), C (= O) (C2-Ce alkenyl), C (= O) O (C2-Ce alkenyl), (C1-C6 alkyl) O (C1-C6 alkyl), (C1-C6 alkyl) OC (= O) (Ci- C6 alkyl), (C1-6 alkyl) S (C1-6 alkyl), (C1-6 alkyl) OC (= O) O (C1-6 alkyl),
[0036] wherein each alkyl, cycloalkyl, cycloalkoxy, alkoxy, alkenyl, and alkynyl are optionally substituted by one or more substituents independently selected from F, Cl, Br, I, CN, NOz, oxo, Cr-Ce alkyl, C.-C, haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-Ce cycloalkoxy, C3-C6 halocycloalkoxy, C1-C6 alkoxy, CrC6 haloalkoxy, S (= O) „(C, -C6 alkyl), S (= OMC, -Ce haloalkyl), OSO2 (C1 -C6 alkyl), OSOsfCi-Ce haloalkyl), C (= O) NRW, (C, -C6 alkyl) NRW, C (= O) (C, -C6alkyl) , C (= O) O (C, -C6 alkyl), C (= O) (C, -C6 haloalkyl), C (= O) O (Ci-Ce haloalkyl), C (= O) (C3-Ce cycloalkyl) ), C (= O) O (C3-C3 cycloalkyl), C (= O) (C2-C6 alkenyl), C (= O) O (C2-C6 alkenyl), (C-C6 alkyl) O (Ci- Cs alkyl), (C, -C and alkyl) S (C1-Cealkyl), C (= O) (C1-Cs alkyl) C (= O) O (C1-C6alkyl), phenyl, and phenoxy;
[0037] (E) R2 is selected from (K), H, CI-CΘalkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C (= O) (Ci-C6alkyl), (Ci- C6 alkyl) O (C1-C6 alkyl), (C1-C6 alkyl) S (C1-C6alkyl), C1-C6 alkylphenyl, C1-Cθ alkyl-O-phenyl, C (= O) (Het-1) , (Het-1), (C1-C6 alkyl) - (Het-1), C1-6 alkyl-OC (= O) C1-6 alkyl, C1-6 alkyl-OC (= O) (C1-6 alkyl), Ci- C6 alkyl-OC (= O) OCi-C6alkyl, C1-6 alkyl-OC (= O) N (RxRy), C1-6 alkylC (= O) N (Rx) C1-6 alkyl- (Het-l ), C1-C6 alkylC (= O) (Het-1), C1-C6 alkylC (= O) N (Rx) C1-C6 alkyl (N (Rx) (Ry)) (C (= O) OH), Ci-C6 alkylC (= O) N (Rx) Ci-Ce alkylN (Rx) (Ry), Ci-Ce alkylC (= O) N (Rx) Ci-Ce alkylN (Rx) C (= O ) -O-C1-C6alkyl, C1-C6 alkylC (= O) N (Rx) C1-C6 alkyl (N (Rx) C (= O) -O-C1-C6 alkyl) (C (= O) OH), Ci-Ce alkylC (-O) (Het-1) C (= O) -O-Ci-Ce alkyl, Ci-Ce alkyl-OC (= O) -O-Ci-Ce alkyl, Ci-Cθ alkyl-OC (= O) Ci-Ce alkyl, Ci-Ce alkyl-OC (= O) C3-C6 cycloalkyl, Ci-C6 alkyl-OC (= O) (Het-1), Ci-C6 alkyl-OC ( = O) C 1 -C 6 alkyl- N (RX) C (= O) -O-C 1 -C 6 alkyl, C 1 -C 6 alkyl-NRxR y, (Ci-Cθ alkyl) S- (Het-l) or Ci-Ce alkyl-O- (Het-l),
[0038] where each alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, and (Het-1) are optionally substituted by one or more substituents independently selected from F, Cl, Br, I, CN, NO2, NRxRy, Cy-Ce alkyl, CI-CΘhaloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, Ca-Ce cycloalkoxy, Cs-Cβ halocycloalkoxy, Ci-Cβ alkoxy, Ci-Cβ haloalkoxy, Ca-Ca alkenyl, Cβ-Cβ cycloalkenyl, Ca-Cβ alkenyl , Ca-Ce cycloalkynyl, S (= O) n (C.-Cβ alkyl), S (= O) „(Ci-Cβ haloalkyl), OSO2 (Ci-C6 alkyl), OSOafCrCa haloalkyl), C (= O) H, C (= O) OH, C (= 0) NRW, (Ci-Cβ alkyl) NRW, C (= O) (C, -Cβ alkyl), C (= O) O (Ci-Cβ alkyl ), C (= O) (Ci-Cβ haloalkyl), C (= O) O (C <-C6 haloalkyl), C (= O) (Ca-Cβ cycloalkyl), C (= O) O (Ca-Cβ cycloalkyl), C (= O) (C2-C6 alkenyl), C (= O) O (C2-Cβ alkenyl), (Ci-Cβ alkyl) O (Ci-Cβ alkyl), (Ci-Cβ alkyl) S (Ci-Cβ alkyl), C (= O) (Ci-Cβ alkyl) C (= O) O (C, -Cβ alkyl), phenyl, phenoxy, Si (Ci-Cβ alkyls, S (= O) nNRxRY , or (Het-1);
[0039] (F) R3is selected from phenyl, Ci-Cβ alkylphenyl, Ci-Cβ alkyl-O-phenyl, Cs-Cβ alkenyl-O-phenyl, (Het-1), Ci-Cβ alkyl (Het-l ), or C1-C6 alkyl-O- (Het-1),
[0040] wherein each alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, and (Het-1) are optionally substituted by one or more substituents independently selected from F, Cl, Br, I, CN, NO2, NRxRy, C-C6 alkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, C1-C6 alkoxy, Ci-C6haloalkoxy, C2-C6 alkenyl, C3-C6 cycloalkenyl, C2-C6 alkyn, S (= O) n (C 1 -C 6 alkyl), S (= O) n (C 1 -C 6 haloalkyl), OSO2 (C 1 -C alkyl), OSO 2 (C 1 -C haloalkyl), C (= O) H, C (= O) NRxRy, (CrCe alkyl) NRxRy, C (= O) (C1-6 alkyl), C (= O) O (C1-6 alkyl), C (= O) (C1-6 haloalkyl), C (= O) O (C-C6 haloalkyl), C (= O) (C3-C6 cycloalkyl), C (= O) O (C3-C6 cycloalkyl), C (= O) (C2-C6 alkenyl), C (= O) O (C2-C6 alkenyl), O (C1-C6 alkyl), S (C1-C6 alkyl), C (= O) (C1-C6 alkyl) C (= O) O (C1-C6 alkyl) ), phenyl, fexy, and (Het-1);
[0041] (G) R4 is selected from (K), H, or CI-CΘalkyl;
[0042] (H) M is N or C-R5,
[0043] where R5 is selected from H, F, Cl, Br, I, CN, NO2, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-Ce cycloalkyl, C3-Ce halocycloalkyl, S (= O) n ( Ci-Ce alkyl), S (= O) n (Ci-Ce haloalkyl), C (= O) NRxRy, C (= O) (Ci-C6 alkyl), C (= O) O (Ci-Cβ alkyl) , C (= O) (C 1 -C 6 haloalkyl), C (= O) O (C 1 -C haloalkyl), C (= O) (C 3 -C cycloalkyl), C (= O) O (C 3 -CΘ cycloalkyl) , C (= O) (C2-C6 alkenyl), C (= O) O (C2-C6 alkenyl), or female;
[0044] (I) (1) Q1 is selected from O or S,
[0045] (2) Q2 is selected from O or S;
[0046] (J) Rx and Ry are independently selected from H, C1 C6alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, S (= O) n ( C1-6 alkyl), S (= O) n (C1-6 haloalkyl), OSO2 (C1-6 alkyl), OSO2 (C1-6 haloalkyl), C (= O) H, C (= O) (Ci-Ce alkyl) ), C (= O) O (Ci-Cβ alkyl), C (= O) (Ci-Cβ haloalkyl), C (= O) O (Ci-C6 haloalkyl), C (= O) (C3-Ce cycloalkyl) ), C (= O) O (C3-C cycloalkyl), C (= O) (C2-C6 alkenyl), C (= O) O (C2-C6 alkenyl), (C-C6 alkyl) O (Ci- Cβ alkyl), (Ci-Cβ alkyl) S (Ci-Ce alkyl), C (= O) (CI-CΘ alkyl) C (= O) O (Ci-C6 alkyl), and phenyl,
[0047] in which each alkyl, cycloalkyl, cycloalkoxy, alkoxy, alkenyl, alkynyl, phenyl, phenoxy, and (Het-1), are optionally substituted by one or more substituents independently selected from F, Cl, Br, I, CN, NO2, OXO, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6halocycloalkoxy, C1-C6 alkoxy, C1-C6haloalkoxy, C-C6haloalkoxy, C2-C6, C2-C3 C6 cycloalkenyl, C2-C6 alkynyl, C3-C6 cycloalkynyl, S (= O) n (Ci-Ce alkyl), S (= O) n (C-C6 haloalkyl), OSO2 (Ci-C6 alkyl), OSO2 (Ci -C6 haloalkyl), C (= O) H, C (= O) OH, C (= O) (C1-C6 alkyl), C (= O) O (C1-C6 alkyl), C (= O) ( C1-6 haloalkyl), C (= O) O (C1-6 haloalkyl), C (= O) (C3-C6 cycloalkyl), C (= O) O (C3-C6 cycloalkyl), C (= O) ( C2-C6 alkenyl), C (= O) O (C2-C6 alkenyl), (Ci-Cθ alkyl) O (Ci-Ce alkyl), (Ci-Ce alkyl) S (Ci-C6 alkyl), C (= O) (C 1 -C 6 alkyl) C (= O) O (C 1 -C 6 alkyl), phenyl, halophenyl, phenoxy, and (Het-1),
[0048] or Rx and Ry together can optionally form a 5- to 7-membered saturated or unsaturated cyclic group that can contain one or more heteroatoms selected from nitrogen, sulfur, and oxygen, and where said cyclic group can be replaced by F, Cl, Br, I, CN, oxo, thioxo, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, C-C6 alkoxy, C1-C6 haloalkoxy , C2-C6 alkenyl, C3-C6 cycloalkenyl, C2-C6 alkynyl, C3-CΘcycloalkynyl, S (= O) n (C1-C6 alkyl), S (= O) n (C1-C haloalkyl), OSO2 (Ci- C6alkyl), OSO2 (C1-C6 haloalkyl), C (= O) (C1-C6alkyl), C (= O) O (C1-C6alkyl), C (= O) (C1-C6 haloalkyl), C (= O ) O (C 1 -C 6 haloalkyl), C (= O) (C 3 -C 6 cycloalkyl), C (= O) O (C 3 -CΘcycloalkyl), C (= O) (C 2 -C alkenyl), C (= O) O (C2-CΘalkenyl), (C1-C6 alkyl) O (C1-C6alkyl), (C1-C6 alkyl) S (C1-C6alkyl), C (= O) (C1-C6 alkyl) C ( = O) O (C 1 -C 6 alkyl), phenyl, substituted phenyl, phenoxy, and (Het-1);
[0049] (K) R2 and R4 together with CX (Q2) (NX), form a 4- to 7-membered hydrocarbyl, saturated or unsaturated cyclic group, which may contain one or more other heteroatoms selected from nitrogen, sulfur, and oxygen,
[0050] wherein said cyclic hydrocarbyl group can optionally be replaced by R6 and R7,
[0051] where R6 and R7 are independently selected from H, F, Cl, Br, I, CN, Ci-Ce alkyl, oxo, thioxo, Ci-Ce haloalkyl, C3-Ce cycloalkyl, C3-CΘhalocycloalkyl, C3-Cβ cycloalkoxy, C3-Cθ halocycloalkoxy, Ci-C6 alkoxy, Ci-Ce haloalkoxy, C2-Ce alkenyl, C3-CΘcycloalkenyl, C2-C6 alkynyl, C3-Cθ cycloalkynyl, S (= O) n (Ci-Ce alkyl), S (= O) n (C-C6 haloalkyl), OSO2 (C1-C6alkyl), OSO2 (C1-C6 haloalkyl), C (= O) (C1-C6alkyl), C (= O) O (C1-C6alkyl), C (= O) (C 1 -C 6 haloalkyl), C (= O) O (C 1 -C 6 haloalkyl), C (= O) (C 3 -C cycloalkyl), C (= O) O (C 3 -C cycloalkyl), C (= O) (C2-C6 alkenyl), C (= O) O (C2-Ce alkenyl), (Ci-Ce alkyl) O (Ci-Ce alkyl), (Ci-Ce alkyl) S (Ci-Ce alkyl), C (= O) (C 1 -C 6 alkyl) C (= O) O (C 1 -C 6 alkyl), phenyl, substituted phenyl, phenoxy, or (Het-1);
[0052] (L) (Het-1) is a 5- or 6-membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms independently selected from nitrogen, sulfur or oxygen, wherein said heterocyclic ring can also be substituted by one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2, oxo, C1-C6 alkyl, CI-CΘhaloalkyl, C3-C6 cycloalkyl, C3-Cβ halocycloalkyl, C3-C6 cycloalkoxy, C3 -C6 halocycloalkoxy, CI-CΘalkoxy, C1-C6 haloalkoxy, C2-C6 alkenyl, C2-C6 alkynyl, S (= O) n (C1-C6 alkyl), S (= O) n (C1-C6 haloalkyl), OSO2 (CI-CΘalkyl), OSÜ2 (C1-C6 haloalkyl), C (= O) NRxRy, (C1-C6 alkyl) NRxRy, C (= O) (Ci-C6alkyl), C (= O) O (Ci-C6alkyl) ), C (= O) (C 1 -C 6 haloalkyl), C (= O) O (C 1 -C 6 haloalkyl), C (= O) (C 3 -C cycloalkyl), C (= O) O (C 3 -C cycloalkyl) ), C (= O) (C2-C6 alkenyl), C (= O) O (C2-C6 alkenyl), (CI-CΘalkyl) O (Ci- C6alkyl), (C1-C6 alkyl) S (C1-C6alkyl) ), C (= O) (Ci-C6 alkyl) C (= O) O (Ci-C6 alkyl), phenyl, phenoxy, substituted phenyl a and substituted phenoxy,
[0053] wherein such substituted phenyl and substituted phenoxy have one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2, CI-CΘalkyl, Ci-Ce haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6halocycloalkoxy, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyl, C2-C6 alkynyl, S (= O) n (Ci-Ce alkyl), S (= O) n (C1-C6 haloalkyl), OSO2 (C1-C6 alkyl), OSθ2 (C1-Cβ haloalkyl), C (= O) H, C (= O) NRxRy, (C1-C6 alkyl) NRxRy, C (= O) (C1-C6alkyl), C (= O) O (C1-C6alkyl), C (= O) (C1-C6 haloalkyl), C (= O) O (C1-C6 haloalkyl), C (= O) (C3-C6 cycloalkyl), C (= O) O (C3-C6 cycloalkyl), C (= O) (C2-C6 alkenyl), C (= O) O (C2-C6 alkenyl), (C1-C6 alkyl ) O (C1-6 alkyl), (C1-6 alkyl) S (C1-6 alkyl), phenyl, and phenoxy; and
[0054] (M) n is each individually 0.1, or 2.
[0055] Many of the molecules of this invention can be described in two or more tautomeric forms such as when R1, R2, or R4, is H (see, for example, the "TAU Scheme" below). With the intention of simplifying the schemes, all molecules have been described as existing as a single tautomer. Any and all alternative tautomers are included within the scope of this invention, and no inference must be made for the molecule to exist as the tautomeric form in which it is represented. “TAU scheme”

[0056] In another modality Ar1 is a substituted phenyl.
[0057] In another embodiment Ar1 is a substituted phenyl that has one or more substituents selected from Ci-Cθ haloalkyl and Ci-Ce haloalkoxy.
[0058] In another modality Ar1 is a substituted phenyl that has one or more substituents selected from CF3, OCF3, and OC2F5.
[0059] In another modality Het is selected from benzofuranyl, benzoylothiazolyl, benzoyloxazolyl, benzoxazolyl, benzothienyl, benzoylthiazolyl cinolinyl, furanyl, indazolyl, indolyl, imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl, oxoxazolyl, isoxazolyl, oxoxazolyl, isoxazolyl, oxazolol, isoxazolyl, oxazolol, oxoxazolol, isoxazolyl, oxazolol, , pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thi- azolinyl, thiazolyl, thienyl, triazinyl, triazolyl, piperazinyl, tyridinyl, pyridinyl, piperidinyl, piperidinyl, piperidinyl, piperidinyl, piperidinyl, piperidinyl , 1,2,3,4-tetrahydro-quinolinyl, 4,5-dihydro-oxazolyl, 4,5-dihydro-1 H-pyrazolyl, 4,5-dihydro-isoxazolyl, and 2 , 3-dihydro- [1,3,4] -oxadiazolyl.
[0060] In another modality Het is triazolyl.
[0061] In another modality Het is 1,2,4 triazolyl.
[0062] In another modality Het is oxadiazolyl.
[0063] In another modality Het is 1,3,4 oxadiazolila.
[0064] In another modality Het is pyrazolyl.
[0065] In another modality Ar2 is phenyl.
[0066] In another modality Ar2 is a substituted phenyl.
[0067] In another embodiment Ar2 is a substituted phenyl that has one or more substituents selected from C1-6 alkyl.
[0068] In another modality Ar2 is the substituted phenyl that has one or more substituents, where said substituent is CH3.
[0069] In another modality R1 is H.
[0070] In another embodiment R2 is (K), H, Ci-Cβ alkyl, CI-CΘalkyl-OC (= O) Ci-C6alkyl, Ci-C6 alkyl-OC (= O) N (RxRy), or (Ci-Cβ alkyl) S- (Het-1).
[0071] In another embodiment R2 is (K), H, CH3, Ci-Ce alkyl, CH2OC (= O) CH (CH3) 2, CH2OC (= O) N (H) (C (= O) OCH2Ph), or CH2S (3,4,5-trimethoxy-2-tetrahydropyran).
[0072] In another modality R3 is substituted phenyl.
[0073] In another embodiment R3 is substituted phenyl, wherein said substituted phenyl has one or more substituents selected from F, Cl, Ci-Ce alkyl, C3-C6 cycloalkyl, Ci-Ce alkoxy, and phenyl.
[0074] In another embodiment R3 is substituted phenyl, wherein said substituted phenyl has one or more substituents selected from F, CH3, 2-CH (CH3) 2, CH (CH3) (C2H5), OCH3, and phenyl.
[0075] In another embodiment R3 is substituted phenyl, wherein said substituted phenyl has more than one substituent and at least one pair of said substituents are not ortho to each other.
[0076] In another modality R3 is Ci-Ce alkylphenyl.
[0077] In another modality R3 is (Het-1).
[0078] In another modality R4 is H.
[0079] In another modality M is N.
[0080] In another modality M is CR5, where R5 is selected from H, CN, and C (= O) (C1-6 alkyl).
[0081] In another modality Q1 is O.
[0082] In another modality Q2 is S.
[0083] In another modality Q2 is O.
[0084] In another modality R2 and R4 are (K), in which R2 and R4 together with CX (Q2) (NX), form a cyclic group of hydrocarbyl, saturated or unsaturated, of 4 to 7 members.
[0085] In another modality R2 and R4 are (K), in which R2 and R4 together with CX (Q2) (NX), form a hydrocarbyl cyclic group, saturated or unsaturated, of 4 to 7 members, in which said group cyclic hydrocarbyl is replaced by oxo or CI-CΘalkyl.
[0086] In another modality R2 and R4 are (K), in which R2 and R4 together with CX (Q2) (NX), form a hydrocarbyl cyclic group, saturated or unsaturated, of 4 to 7 members, in which the “bond ”Between Q2 and Nx is CH2C (= O), CH2CH2, CH2CH2CH2, or CH2CH (CH3).
[0087] The molecules of this invention will generally have a molecular mass of about 400 Daltons to about 1200 Daltons. However, it is generally preferred if the molecular mass is from about 300 Daltons to about 1000 Daltons, and it is even more generally preferred if the molecular mass is from about 400 Daltons to about 750 Daltons. PREPARATION OF TRIARILLA INTERMEDIARIES
[0088] The molecules of this invention can be prepared by producing a triaryl intermediate, Ar1-Het-Ar2, and then linking it to a desired intermediate to form a desired compound. A wide variety of triaryl intermediates can be employed to prepare its molecules, provided that such triaryl intermediates contain a suitable functional group in Ar2 to which the rest of the desired intermediate can be attached. Suitable functional groups include an amino or isocyanate or a carboxyl group. These triaryl intermediates can be prepared by methods previously described in the chemical literature, including Crouse, and other (s), PCT Int. Appl. Publ. W02009 / 102736 A1 (the total description of which is incorporated by reference). PREPARATION OF UREA BINDING COMPOUNDS
[0089] The thiobiurides (thio-bisureas) and biurets can be prepared according to Scheme 1, Scheme 2, and Scheme 3, described as follows. The precursors of S-R2 thiourea (3) are prepared from the corresponding thiourea (1) by treatment with R2-X, where X is a halogen or methanesulfonate or a similar displaceable group. These are normally isolated as their hydroalide (methanesulfonate) salts. The subsequent treatment of the S-R2 precursors thiourea (3) with an isocyanate (4) (see, for example, Pandey, AK; and other (s), Ind J. Chem., Sect. B: Org. Chem. Incl Med. Chem. (1982), 21B (2), 150-2) or with a p-nitrophenyl carbamate, such as (5), in the presence of a base, such as triethylamine or potassium carbonate or cesium carbonate , results in the formation of an S-alkyl thiobiuride (6). Layout 1

[0090] When R2 is -CH2OC (O) alkyl, treatment with ethanolic HCI at temperatures from about 0 ° C to about 50 ° C, results in the removal of R2 and generation of the thiobiuride (7) (Scheme 2). Under longer heating, for example, by heating in ethanolic HCI at reflux temperature for about 1 to about 24 hours, the thiobiuret is converted to a biuret (8), with oxygen replacing the sulfur atom. Layout 2

[0091] An alternative process for forming thiobiurides has been described by Kaufmann, HP; Luthje, K. (Archiv Pharm. Und Ber. Deutschen Pharm. (1960), 293, 150-9) and Oertel, G., and others (Farb. Bayer, DE 1443873 A 19681031 (1972). An isothiocyanate carbamoyl (9) is treated with an aniline equivalent to form (7) (Scheme 3). Yet another route for thiobiurides involves the treatment of an N-aryl urea with R3-NCS (N. Siddiqui, and another (s ), Eur. J. Med. Chem., 46 (2011), 2236-2242) Another route for biurets (8) involves the treatment of an N-aryl urea with R3 isocyanate (Briody, and others (s), J. Chem. Soc., Perk. 2, 1977, 934-939).

[0092] Thiobiurides (7) can be converted into a variety of cyclized analogues (10) by treatment with, for example, vicinal dialects (for example, 1-bromo-2-chloroethane, to form 2-imino-1, 3-thiazolines (10a)), or with methyl bromoacetate (to form 2-imino 1,3-thiazolin-4-ones (10b)), or with Q-halo ketones (to form 2-imino-1,3- thiazoles (10c)), as described in Scheme 4. A base such as potassium carbonate or sodium acetate, in a protic solvent or aprotic solvent, at temperatures between about 0 ° C and about 100 ° C, can be employed. Using the conditions described above, it can be seen that other ring sizes and replacements can be envisaged as well; the corresponding six-membered ring analog (10d), for example, can be prepared starting with a 1,3-dialopropane precursor. Layout 4

[0093] An alternative route for the analogs of Formula (10b) is described in Scheme 5. Treatment of 2-imino-1,3-thiazolin-4-one (11) with an aryl isocyanate or with the intermediate (5 ) (Scheme 1), in the presence of an amine base such as triethylamine, induces the synthesis of (10b). Other pathways for (10b) include adding carbonyl diimidazole to (11) to produce an intermediate (12a), or adding 4-nitrophenyl chloroformate to form (12b). (12a) or (12b) can then be made to react with an Ar1-Het-Ar2-NH2 aniline to generate (10b). Layout 5

[0094] Another route for 1- (3-aryl thiazolidin-2-ylidene) -3-aryl ureas (10a) is shown in Scheme 6. Treatment of an aryl cyanamide (12) with a thyrane in the presence of such a base as potassium carbonate it produces 2-imino-1,3-thiazoline (14). The synthesis and subsequent acylation of 3-aryl-2-iminothiazolidines by this route is described by FX Woolard in US 4,867,780 and the references contained therein. Subsequent treatment of (14) with carbonyldiimidazole (to form 15a) or 4-nitrophenyl chloroformate (to form 15b), followed by the addition of an aniline results in the formation of (10a). Alternatively, the reaction of (14) with an aryl isocyanate or 4-nitrophenyl carbamate (5) also produces (10a). Layout 6

[0095] Using the protocols described in Schemes 4 through 6, it can be seen that other analogs containing 4-, 5-, and 6-member rings, and containing a variety of substitution patterns, can be produced. Other heterocyclic systems containing an exo-imino group are known, including but not limited to, 2-imino thiadiazolinones (16) (see Scheme 7); or 2-imino oxadiazolines (17) (Syn. Comm., 2002, 32 (5), 803-812); or 2-imino oxazolines (18); or 2-imino thiadiazoles (19). These can also be used to prepare molecules (20) - (23), by appropriate replacement of precursors in the procedures described in Scheme 5 and Scheme 6. Scheme 7

[0096] Malonyl monothioamides ((25) and (26)) and malonyl diamides (29) can be prepared as described in Scheme 8. Condensation of a β-ketoanilide or a-cyanoanilide (24) with R3-NCS results in the formation of 2-acyl malono-monothioamide (25). When R5 is an acetyl group, deacylation occurs at reflux in EtOH to form malono-monothioamide (26). Thioamides can be cyclized in a manner similar to that described in Schemes 5 and 6, to produce cyclic analogues (27). The diamide (29) can be prepared from the corresponding monocarboxylic acid (28), by means of coupling conditions of dicyclohexyl carbodiimide-1-hydroxy 7-azabenzotriazole. (For example, see Jones, J., in: The Chemical Synthesis of Peptides. Int. Ser. Of Monograi 'e ~ g', Oxford Univ. (Oxford, 1994), 23).

[0097] Other alkylation modifications of the NH group of analogs such as (6), (10a), (10b), (10c), (20) - (23), and (27) can be made by treating the appropriate molecule with an alkylating agent, R1-X, where X is a halogen or methanesulfonyl group, or another similar leaving group (Scheme 9). The reaction requires the use of a strong base such as sodium hydride (NaH) or potassium hexamethyldisilazane, in an aprotic solvent such as tetrahydrofuran or / V, A / -dimethylformamide. Scheme 9

[0098] Analogs, where R1 is not H can also be prepared as shown in Scheme 10. Alkylation of Ar1-Het-Ar2-NH2, and conversion to thiourea (31), can be performed by a variety of known methods, for example, reaction with formaldehyde and benzotriazole, followed by reduction with sodium borohydride, generates the analog of A / -methyl (30). Conversion to (31) can be performed by treatment with thiophosgene and ammonia, or with benzoyl isothiocyanate followed by cleavage catalyzed by the benzoyl group. The treatment of (31) with oxalyl chloride and triethylamine, under the first conditions described by J. Goerdeler and K. Jonas (Chem. Ber., 1966, 99 (11), p. 3572-3581), results in the formation of a 2-amino-1,3-thiazolin-4,5-dione (32). The pyrolysis of this intermediate in refluxing toluene then generates an A / -carbonyl isothiocyanate (33), which upon treatment with an R3-NH2 amine forms the thiobiuride (7b, R1 = CH3). Thiobiurides where R1 is not H can then also be elaborated using the conditions described in Scheme 4, to form the cyclic analogues such as 10e. Layout 10

[0099] An aryl isocyanate, Ar1-Het-Ar2-NCO, can also be treated directly with an A / -aryl thiourea in the presence of a catalytic amount of base such as cesium carbonate or sodium hydride, resulting in the formation of a thiobiuret (7) (Scheme 11). Layout 11

[00100] A method for preparing 1- (Ar1) -3- (Ar2) -1,2,4-triazols (36), Ar1 is a 4- (haloalkoxy) phenyl or 4- (haloalkyl) phenyl group, the coupling 1- (4-haloalkoxy) phenyl-3-bromo-1,2,4-triazole or 1- (4-haloalkyl) phenyl-3-bromo-1,2,4-triazole (35, Scheme 12) with an aryl boronic acid or aryl boronic ester, under Suzuki conditions. Intermediates (35) can also be prepared by reacting 3-bromo-1H-1,2,4-triazole (Kroeger, CF; Miethchen, R., Chemische Berichte (1967), 100 (7), 2250) (therefore 3-chloro-1H-1,2,4-triazole can be used) with a 4-haloalkoxy-1-halobenzene (where halo = independently I or Br or Cl or F), in the presence of such a metal catalyst such as Cul or CU2O, and a base such as CS2CO3, K3PO4, or K2CO3, with or without an added linker such as quinolin-8-ol, or A /, A / '- dimethyl ethylenediamine or other 1,2-diamines, or glycine, in a polar aprotic solvent such as acetonitrile, DMF or DMSO at temperatures between about 70 and 150 ° C. Layout 12

[00101] New 1-Ar1-3-bromo-1,2,4-triazoles have also been described, where Ar1 is 4- (C1-C6-alkyl) phenyl, 4- (C1-C6-haloalkyl) phenyl, 4 - (CI-CΘalkoxy) phenyl, 4- (Ci-C6-haloalkoxy) phenyl, 4- (Ci-Ce alkylthio) phenyl, or 4- (Ci-C6-haloalkylthio) phenyl, as useful intermediates for the preparation of many molecules claimed in this invention (the preparation is described in Scheme 12.
EXAMPLES
[00102] The examples are for illustrative purposes and are not to be construed as limiting the invention described in this document to only the modalities described in these examples.
[00103] The starting materials, reagents, and solvents that were obtained from commercial sources were used without further purification. Anhydrous solvents were purchased as Sure / Seal ™ from Aldrich and were used as received. Melting points were obtained on an OptiMelt automated melting point system from Stanford Research Systems and are uncorrected. The molecules are provided with their known names, named according to the naming programs within MDL ISIS ™ / Draw 2.5, ChemBio-Draw Ultra 12.0 or ACD Name Pro. If such programs are unable to name a molecule, the molecule is named using conventional naming rules. The data for 1H NMR spectra are in ppm (δ) and were recorded at 400 MHz, unless otherwise stated. Example 1. Preparation of (E) - ((A / * - (4-methoxy-2-methylphenyl) - / V - ((4- (1 - (4- (trifluoromethyl) phenyl) -1 H-1 isobutyrate , 2,4-triazol-3-yl) phenyl) carbamoyl) carbamimidoyl) thio) methyl (Molecule A1).

[00104] Step 1. 2-Methyl-4-methoxyphenyl thiourea (0.5 gram (g), 2.55 millimoles (mmol)) and bromomethyl isobutyrate were combined in 5 ml of acetone at room temperature, and the solution was allowed to stir for 18 hours (h). The solution was then cooled to 0 ° C and the resulting solid was filtered and air dried to provide the HBr (B1) methyl (E) - (A / '- (4-methoxy-2-methylphenyl) carbamimidoiltio) isobutyrate (0.83 g, 82%): melting point 127 to 130 ° C; 1H NMR (CDCh) δ 11.34 (s, 1H), 10.29 (s, 1H), 8.32 (s, 1H), 7.09 (d, J = 8.7 Hz, 1H), 6 , 79 (d, J = 2.8 Hz, 1H), 6.74 (dd, J = 8.7, 2.8 Hz, 1H), 3.81 (s, 3H), 2.69 (heptide, J = 7.0 Hz, 1H), 2.31 (s, 3H), 1.22 (d, J = 7.0 Hz, 6H); ESIMS m / z 297 ([M + H] +).
[00105] Step 2. The intermediate from step 1 (0.40 g, 1.06 mmol) was dissolved in tetrahydrofuran (THF; 7 ml_), and 4- (1- (4- (trifluoro-methyl) phenyl) ) -1 / - / - 1,2,4-triazol-3-yl) 4-nitrophenyl phenylcarbamate (0.50 g, 1.06 mmol) was added. To this suspension was added A / -ethyl- / V-isopropylpropan-2-amine (Hünig's base; 0.25 g, 1.9 mmol), and the solution was allowed to stir at room temperature for 2 hours. Evaporation of the volatiles left a viscous oil which was purified by chromatography on silica gel. Elution with 0 to 50% ethyl acetate (EtOAc) -hexanes provided the title compound (425 mg, 61%) as a white solid: melting point 160 to 164 ° C; 1H NMR (CDCh) δ 11.24 (s, 1H), 8.64 (s, 1H), 8.17 (d, J = 8.7 Hz, 2H), 7.92 (d, J = 8, 4 Hz, 2H), 7.80 (d, J = 8.5 Hz, 2H), 7.67 (d, J = 8.7 Hz, 2H), 7.41 (s, 1H), 7.12 (d, J = 8.6 Hz, 1H), 6.79 (d, J = 2.8 Hz, 1H), 6.74 (dd, J = 8.4, 3.1 Hz, 1H), 5 , 65 (s, 2H), 3.82 (s, 3H), 2.59 (heptet, J = 7.0 Hz, 1H), 2.27 (s, 3H), 1.18 (d, J = 7.0 Hz, 6H); ESIMS m / z 627 ([M + H] +).
[00106] The A54-A62 molecules in Table 1 were made according to the procedures described in example 1. The following molecules (Examples 2-10) were prepared according to the conditions described in example 1. Example 2. / V- (4-methoxy-2-methylphenyl) - / V '- ((4- (1- (4- (trifluoro-methyl) phenyl) -1H-1,2,4-triazol-3-yl) phenyl) carbamoyl) (Z) -Methyl carbamimidothioate (Molecule A2).

[00107] The title molecule was isolated as a white solid; 38 mg (11%), melting point 172 to 175 ° C; 1H NMR (CDCh) δ 11.29 (s, 1H), 8.64 (s, 1H), 8.17 (d, J = 8.7 Hz, 2H), 7.92 (d, J = 8, 5 Hz, 2H), 7.80 (d, J = 8.5 Hz, 2H), 7.66 (d, J = 8.7 Hz, 2H), 7.33 (s, 1H), 7.16 (d, J = 8.6 Hz, 1H), 6.80 (d, J = 2.9 Hz, 1H), 6.75 (dd, J = 8.6, 2.8 Hz, 1H), 3 , 82 (s, 3H), 2.38 (s, 3H), 2.30 (s, 3H); ESIMS m / z 541 ([M + H] +). Example 3. (E) - (Ar- (2,6-Dimethylphenyl) - / V- (4- (1- (4- (trifluoromethyl) phenyl) -1 H-1,2,4-triazole-isobutyrate -yl) phenylcarbamoyl) carbamimido-thio) methyl (Molecule A3).

[00108] Step 1. The (E) - (A / '- (2,6-dimethylphenyl) carbamimidoylthio) methyl (B2) HBr intermediate was prepared from 1- (2,6-dimethylphenyl thiourea) using the conditions described in Example 1. the melting point of 129 to 131 ° C; 1H NMR (CDCh) δ 11.51 (s, 1H), 10.45 (s, 1H), 8.25 (s, 1H), 7.23 (d, J = 7.5 Hz, 1H), 7 , 12 (d, J = 7.4 Hz, 2H), 5.59 (s, 2H), 2.69 (heptet, J = 7.0 Hz, 1H), 2.30 (s, 6H), 1 , 23 (d, J = 7.0 Hz, 6H); ESIMS m / z 280 ([M + H] +).
[00109] Step 2. Molecule A3 was prepared in a similar manner to that described in example 1: 575 mg (59%) of a solid, melting point 173 to 176 ° C; 1H NMR (CDCh) δ 11.21 (s, 1H), 8.65 (s, 1H), 8.18 (d, J = 8.7 Hz, 2H), 7.92 (d, J = 8, 4 Hz, 2H), 7.80 (d, J = 8.5 Hz, 2H), 7.68 (d, J = 8.7 Hz, 2H), 7.20 (m, 1H), 7.14 - 7.04 (m, 2H), 5.65 (s, 2H), 2.59 (heptet, J = 7.0 Hz, 1H), 2.29 (s, 6H), 1.18 (d, J = 7.0 Hz, 6H); ESIMS m / z 611 ([M + H] +). Example 4. (E) - (/ f- (2,6-Dimethylphenyl) - / V- (4- (1- (4- (trifluoromethyl-xi) phenyl) -1H-1,2,4-triazole- 3-yl) phenylcarbamoyl) carbamimidothio) methyl isobutyrate (Molecule A4).

[00110] Molecule A4 was prepared in a similar manner to that described in example 1: 860 mg (52%) of a solid, melting point 148 to 151 ° C; 1H NMR (CDCh) δ 11.21 (s, 1H), 8.55 (s, 1H), 8.17 (d, J = 8.7 Hz, 2H), 7.81 (d, J = 8, 7 Hz, 2H), 7.67 (d, J = 8.7 Hz, 2H), 7.42 (br s, 1H), 7.39 (d, J = 8.7 Hz, 2H), 7, 21 - 7.10 (m, 3H), 5.65 (s, 2H), 2.67 - 2.52 (m, 1H), 2.29 (s, 6H), 1.18 (d, J = 7.0 Hz, 6H); ESIMS m / z 627 ([M + H] +). Example 5. (Z) - ((N- (2-lsopropylphenyl) -A / * - ((4- (1- (4- (trifluoromethoxy) phenyl) phenyl) -1H-1,2,4-triazole-isobutyrate -yl) phenyl) carbamoyl) carbamimidoyl) thio) methyl (Molecule A5).

[00111] Step 1. The HBr isobutyrate intermediate of (E) - (/ V '- (2-isopropylphenyl) carbamimidoylthio) methyl (B3), was prepared from 1- (2-isopropylphenyl thiourea) using the conditions described in Example 1; melting point of 80 to 85 ° C; 1H NMR (CDCh) δ 11.70 (s, 1H), 10.45 (s, 1H), 8.27 (s, 1H), 7.47-7.36 (m, 1H), 7.23 m , 1H), 7.15 (d, J = 7.4 Hz, 2H), 5.59 (s, 2H), 3.17 (m, 1H), 2.69 (heptide, J = 7.0 Hz , 1H), 1.26 (d, J = 6.9 Hz, 3H), 1.22 (d, J = 6.9 Hz, 3H); ESIMS m / z 295 ([M + H] +).
[00112] Step 2. The A5 molecule was prepared in a similar manner to that described in example 1: 382 mg (62%) of a solid, melting point 141 to 143 ° C; 1H NMR (CDCh) δ 11.54 (s, 1H), 8.55 (d, J = 3.7 Hz, 1H), 8.16 (d, J = 8.6 Hz, 2H), 7.80 (d, J = 9.1 Hz, 2H), 7.67 (d, J = 8.6 Hz, 2H), 7.46 - 7.32 (m, 5H), 7.23 - 7.16 ( m, 2H), 5.67 (s, 2H), 3.25 - 3.10 (m, 1H), 2.65 - 2.52 (m, 1H), 1.24 (d, J = 6, 9 Hz, 6H), 1.17 (d, J = 7.0 Hz, 6H); ESIMS m / z 641 ([M + H] +). Example 6. (Z) - ((N- (2-lsopropylphenyl) -N '- ((4- (1- (4- (pentafluoroethoxy) phenyl) phenyl) -1 H-1,2,4-triazole-isobutyrate -yl) phenyl) carbamoyl) carbamimidoyl) thio) methyl (Molecule A6).

[00113] The A6 molecule was prepared in a similar manner to that described in example 1: 300 mg (45%) of a solid, melting point of 154 to 156 ° C; 1H NMR (CDCh) δ 11.54 (s, 1H), 8.56 (d, J = 3.7 Hz, 1H), 8.17 (d, J = 8.7 Hz, 2H), 7.81 (d, J = 9.1 Hz, 2H), 7.67 (d, J = 8.7 Hz, 2H), 7.46 - 7.33 (m, 5H), 7.24 - 7.19 ( m, 2H), 5.67 (s, 2H), 3.29 - 3.08 (m, 1H), 2.66 - 2.50 (m, 1H), 1.24 (d, J = 6, 9 Hz, 6H), 1.17 (d, J = 7.0 Hz, 6H); ESIMS m / z 691 ([M + H] +). Example 7. (E) - (N '- (2,6-Dimethyl-4-methoxyphenyl) -N- (4- (1 - (4- (trifluoromethioxy) phenyl) -1 H-1,2,4 isobutyrate -triazol-3-yl) phenylcarbamoyl) carbamimidothio) methyl (Molecule A7).

[00114] Step 1. The HBr isobutyrate intermediate of (E) - (A / '- (2,6-dimethyl-4-methoxyphenyl) carbamimidoylthio) methyl (B4), was prepared from 1- (2,6-dimethyl- 4-methoxyphenyl thiourea) using the conditions described in Step 1 of Example 1: melting point 152 to 154 ° C; 1H NMR (CDCh) δ 6.62 (s, 2H), 5.59 (s, 2H), 3.79 (s, 3H), 2.68 (heptide, J = 7.0 Hz, 1H), 2 , 25 (s, 6H), 1.22 (d, J = 7.0 Hz, 6H); ESIMS m / z 311 ([M + H] +).
[00115] Step 2. The A7 molecule was prepared in a similar manner to that described in example 1: 955 mg (71%) of a solid, melting point from 148 to 151 ° C; 1H NMR (CDCh) δ 11.03 (s, 1H), 8.55 (s, 1H), 8.16 (d, J = 8.7 Hz, 2H), 7.80 (d, J = 9, 1 Hz, 2H), 7.67 (d, J = 8.7 Hz, 2H), 7.39 (m, 3H), 6.64 (s, 2H), 5.64 (s, 2H), 3 , 80 (s, 3H), 2.59 (heptet, J = 7.0 Hz, 1H), 2.25 (s, 6H), 1.17 (d, J = 7.0 Hz, 6H); ESIMS m / z 657 ([M + H] +). Example 8. (Z) - (((benzyloxy) carbonyl) amino) acetate - ((W- (2,6-Dimethylphenyl) -N '- ((4- (1 - (4- (trifluoromethyl) phenyl) -1 H-1,2,4-triazol-3-yl) phenyl) carbamoyl) carbamimidoyl) thio) methyl (Molecule A8).

The intermediate, 2 - (((benzyloxy) carbonyl) amino) ((A / - (2,6-dimethylphenyl) carbamimidoyl) thio) methyl HCI acetate (B5), was prepared as described in Step 1 of the Example 1, and was used without purification. The A8 molecule (30 mg, 15%) was isolated as a white solid, melting point 142 to 148 ° C; 1H NMR (CDCh) δ 11.26 (s, 1H), 8.64 (s, 1H), 8.16 (d, J = 8.4 Hz, 2H), 7.91 (d, J = 8, 2 Hz, 2H), 7.79 (d, J = 8.5 Hz, 2H), 7.71 (d, J = 8.1 Hz, 2H), 7.54 (s, 1H), 7.34 (m, 5H), 7.15 (m, 3H), 5.69 (s, 2H), 5.23 (s, 1H), 5.13 (s, 2H), 4.02 (d, J = 5.7 Hz, 2H), 2.29 (s, 6H); ESIMS m / z 732 ([M + H] +). Example 9. 2 - (((benzyloxy) carbonyl) amino) (E) - ((N '- (4-Methoxy-2,6-dimethylphenyl) - / V - ((4- (1 - (4- (trifluoromethyl) phenyl) -1 H-1,2,4-triazol-3-yl) phenyl) carbamoyl) carbamimidoyl) thio) methyl (Molecule A9).

[00117] The intermediate, 2 - (((benzyloxy) carbonyl) amino) HCI of ((A / - (2,6-dimethyl-4-methoxyphenyl) carbamimidoyl) thio) methyl (B6), was prepared as in Step 1 of Example 1, and was used without purification. The A9 molecule (330 mg, 46%) was isolated as a white solid, melting point 142 to 148 ° C; 1H NMR (CDCh) δ 11.07 (s, 1H), 8.55 (s, 1H), 8.15 (d, J = 8.5 Hz, 2H), 7.80 (d, J = 8, 8 Hz, 2H), 7.70 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 3.1 Hz, 1H), 7.44 - 7.31 (m, 7H) , 6.64 (s, 2H), 5.67 (s, 2H), 5.23 (s, 1H), 5.12 (s, 2H), 4.02 (d, J = 5.8 Hz, 2H), 3.80 (s, 3H), 2.21 (s, 6H); ESIMS m / z 778 ([M + H] +). Example 10. / V- (4-methoxy-2-methylphenyl) -A / '- ((4- (1- (4- (trifluoro-methoxy) phenyl) -1 H-1,2,4-triazole-3 -yl) phenyl) carbamoyl) (Z) carbamimidothioate - ((((2S, 3R, 4ft, 5S, 6S) -3,4,5-Trimethoxy-6-methyl-tetrahydro-2H-pyran-2 -yl) thio) methyl (Molecule A10).

[00118] The intermediate, (4-methoxy-2-methylphenyl) carbamimidothioate HCI of ((((2S, 3R, 4R, 5S, 6S) -3,4,5-trimethoxy-6-methyltetrahydro-2H-pyran- 2-yl) thio) methyl (B7), was prepared as in Step 1 of Example 1, and was used without purification. The A10 molecule (240 mg, 43%) was isolated as a white solid, melting point 128 to 132 ° C; 1H NMR (CDCh) δ 11.19 (s, 1H), 8.56 (s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 7.80 (J = 8.4Hz, 2H), 7.66 (d, J = 8.5 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 7.14 (d, J = 8.6 Hz, 1H) , 6.82 - 6.69 (m, 3H), 5.69 (s, 1H), 4.46 (d, J = 13.9 Hz, 1H), 4.05 (d, J = 13.9 Hz, 1H), 3.91 (dd, J = 9.3, 6.2 Hz, 1H), 3.81 (s, 3H), 3.67 (dd, J = 3.2, 1.5 Hz , 1H), 3.56 (s, 3H), 3.46 s, 3H), 3.44 (s, 3H), 3.38 (dd, J = 9.3, 3.3 Hz, 1H), 3.21 (t, J = 9.3 Hz, 1H), 2.29 (s, 3H), 1.32 (d, J = 6.1 Hz, 3H); ESIMS m / z 777 ([M + H] +). Example 11. Preparation of W - [[(2,6-dimethylphenyl) amino] thioxomethyl] - - (4- (trifluoromethioxy) phenyl) -1 H-1,2,4-triazol-3-yl) phenyl urea (Molecule A11).

[00119] To a solution of the A4 molecule (660 mg, 1.05 mmol) in 75 mL of MeOH was added 20 mL of 1 N HCI, and the resulting solution was heated at 55 ° C for 36 hours. The cooled solution was then diluted with another 50 ml of water and the resulting white solid was filtered and air dried to provide 470 mg (81%) of the title compound, melting point 233 to 235 ° C. 1H NMR (CDCh) δ 8.54 (s, 1H), 8.12 (d, J = 8.7 Hz, 2H), 7.79 (d, J = 9.1 Hz, 2H), 7.62 (d, J = 8.8 Hz, 2H), 7.44 - 7.29 (m, 4H), 7.22 (d, J = 7.5 Hz, 2H), 4.01 (s, 2H) , 2.17 (s, 6H); ESIMS m / z 527 ([M + H] +).
[00120] Compounds A44 and A49-A52 in Table 1 were made according to the procedures described in example 11. Example 12. Preparation of W - [[(2,6-dimethylphenyl) amino] thioxomethyl] - Af- (4 - (1 - (4- (trifluoromethyl) phenyl) -1 H-1,2,4-triazol-3-yl) phenyl urea (Molecule A12).

[00121] To a solution of the A3 molecule (125 mg, 0.203 mmol) in 5 ml of MeOH was added 0.5 ml of 7 N NH3 in MeOH. The resulting solution was allowed to stir at room temperature for 16 hours. The solution was concentrated and chromatographed (0-100% EtO-Ac-hexanes) to provide 28 mg (27%) of the thiobiuride as a white solid, melting point 204 to 212 ° C. 1H NMR (DMSO-dθ) δ 11.30 (s, 1H), 10.20 (s, 1H), 9.52 (s, 1H), 9.51 (s, 1H), 8.19 (d, J = 8.4 Hz, 2H), 8.11 (d, J = 8.7 Hz, 2H), 7.99 (d, J = 8.6 Hz, 2H), 7.62 (d, J = 8.8 Hz, 2H), 7.20 - 7.09 (m, 3H), 2.20 (s, 6H); ESIMS m / z 511 ([M + H] +). Example 13. Preparation of 1- (2-isopropylphenyl) -3 - [[4- [1- [4- (trifluoromethoxy) phenyl] -1,2,4-triazol-3-yl] phenyl] carbamoyl] urea (MoleculeA13).

[00122] The A5 molecule (500 mg, 0.78 mmol) was added to 10 ml of THF and 2 ml of 1 N HCI and the solution was stirred for 24 hours. The solution was then partitioned between EtOAc (30 ml) and saturated NaHCOa solution (15 ml). Separation and drying of the organic layer followed by removal of the solvent provided a crude solid which was chromatographed on silica gel to provide 160 mg (38%) of the title compound as a white solid; melting point 300 ° C (dec); 1H NMR (DMSO-dθ) δ 9.86 (s, 1H), 9.57 (s, 1H), 9.37 (d, J = 13.8 Hz, 2H), 8.15 - 7.98 ( m, 4H), 7.74 (dd, J = 7.9, 1.5 Hz, 1H), 7.67 - 7.53 (m, 4H), 7.33 (dd, J = 7.5, 1.8 Hz, 1H), 7.24 - 7.06 (m, 2H), 3.20 - 2.99 (m, 1H), 1.22 (d, J = 6.8 Hz, 6H). ; ESIMS m / z 525 ([M + H] +). Example 14. Preparation of (Z) -1- (3- (2,6-dimethylphenyl) -4-oxothiazolidin-2-ylidene) -3- (4- (1 - (4- (trifluoromethoxy) phenyl) - 1 H-1,2,4-triazol-3-yl) phenyl) urea (Molecule A14).

[00123] To a suspension of the A11 molecule (200 mg, 0.38 mmol) in 5 ml of EtOH was added sodium acetate (200 mg, 2.43 mmol) and methyl bromoacetate (0.14 g, 0.91 mmol), and the solution was heated to 60 ° C for 3 hours. The cooled solution was then diluted with 2 ml of water and the resulting white solid was filtered and air dried to provide 142 mg (64%) of the title compound, melting point 190 to 196 ° C. 1H NMR (CDCh) δ 8.54 (s, 1H), 8.12 (d, J = 8.7 Hz, 2H), 7.79 (d, J = 9.1 Hz, 2H), 7.62 (d, J = 8.8 Hz, 2H), 7.44 - 7.29 (m, 4H), 7.22 (d, J = 7.5 Hz, 2H), 4.01 (s, 2H) , 2.17 (s, 6H); ESIMS m / z 567 ([M + H] +).
[00124] Compounds A35-A37, A65, A66, A69, A74-A77, A85-A88, A92-A95, A103-A105, A108-A111, A115, A117, A120-A121, and A125 in Table 1 were made according to the procedures described in example 14. Example 15. Preparation of (Z) -2 - ((2,6-dimethylphenyl) imino) -W- (4- (1- (4- (trifluoromethoxy) phenyl) -1H -1,2,4-triazol-3-yl) phenyl) thiazolidine-3-carboxamide (Molecule A15).

[00125] To a solution of the A11 molecule (350 mg, 0.665 mmol) in 7 ml_ of acetone was added potassium carbonate (200 mg, 1.44 mmol) and 1-chloro-2-bromoethane (0.20 g, 1 , 40 mmol), and the solution was heated to 50 ° C for 5 hours. The cooled solution was absorbed on silica gel and chromatographed (0-80% EtOAc-hexanes) to provide 99 mg (26%) of the A15 molecule: melting point 145 at 150 ° C. 1H NMR (CDCh) δ 8.51 (s, 1H), 8.07 (d, J = 7.9Hz, 2H), 7.81 - 7.74 (m, 2H), 7.59 (d, J = 6.8 Hz, 2H), 7.36 (d, J = 8.3 Hz, 2H), 7.19 (m, 3H), 7.12 (s, 1H), 3.81 (t, J = 7.7 Hz, 2H), 3.37 (t, J = 7.6 Hz, 2H), 2.23 (s, 6H); ESIMS m / z 553 ([M + H] +). Example 16. Preparation of (Z) -2 - ((2,6-dimethylphenyl) imino) -W- (4- (1- (4- (trifluoromethoxy) phenyl) -1 H-1,2,4-triazole- 3-yl) phenyl) -1,3-thiazinane-3-carboxamide (Molecule A16).

[00126] To a solution of the A11 molecule (150 mg, 0.28 mmol) in 5 ml of acetone was added potassium carbonate (150 mg, 1.08 mmol) and 1-chloro-3-bromopropane (0.16 g , 1.00 mmol), and the solution was heated to 50 ° C for 5 hours. The cooled solution was absorbed on silica gel and chromatographed (0 to 70% EtOAc-hexanes) to provide 22 mg (12%) of thiazinane: melting point of 121 to 125 ° C. 1H NMR (CDCh) δ 12.81 (s, 1H), 8.54 (s, 1H), 8.16 - 8.09 (m, 2H), 7.79 (d, J = 9.2 Hz, 2H), 7.63 (d, J = 8.8 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 7.18 - 6.96 (m, 3H), 4, 22 - 4.09 (m, 2H), 3.00 (t, J = 6.9 Hz, 2H), 2.25 - 2.13 (m, 8H); ESIMS m / z 567 ([M + H] +).
[00127] Compounds A39 and A41 in Table 1 were made according to the procedures described in example 16. Example 17. Preparation of (Z) -2 - ((2,6-dimethylphenyl) imino) - / V- (4 - (1- (4- (trifluoromethoxy) phenyl) -1H-1,2,4-triazol-3-yl) phenyl) thiazolidine-3-carboxamide (Molecule A17).

[00128] To a solution of Molecule A11 (150 mg, 0.28 mmol) in 5 mL of acetone was added potassium carbonate (100 mg, 0.72 mmol) and 1,2-dibromopropane (0.07 g, 1 , 20 mmol), and the solution was heated to 50 ° C for 12 hours. The cooled solution was absorbed on silica gel and chromatographed (0 to 80% EtOAc-hexanes) to provide 29 mg (18%) of the title compound as a light brown solid; melting point 105 to 115 ° C. 1H NMR (CDCh) δ 8.52 (s, 1H), 8.07 (d, J = 8.3 Hz, 2H), 7.83 - 7.73 (m, 2H), 7.59 (d, J = 8.2 Hz, 2H), 7.37 (d, J = 8.3 Hz, 2H), 7.20 (m, 4H), 4.24 (dd, J = 14.5, 6.6 Hz, 1H), 3.58 - 3.41 (m, 4H), 3.02 (dd, J = 11.0, 8.6 Hz, 1H), 2.25 (s, 3H), 2.21 (s, 3H), 1.21 (d, J = 6.4 Hz, 3H); ESIMS m / z 567 ([M + H] +).
[00129] Compounds A38 and A40 in Table 1 were made according to the procedures described in example 17. Example 18. Preparation of (Z) -1- (3- (2- (sec-butyl) phenyl) -4- oxothiazolidin-2-ylidene) -3- (4- (1 - (4- (trifluoromethoxy) phenyl) -1 H-1,2,4-triazol-3-yl) phenyl) urea (Molecule A18).

[00130] To a solution of 1- (2- (sec-butyl) phenylthiourea (1.40 g, 6.72 mmol) suspended in 5 ml of acetone was added methyl bromoacetate (1.23 g, 1.20 mmol ), and the solution was allowed to stir at room temperature for 18 hours.The solution was then diluted with 8 ml of diethyl ether and, after stirring for 30 minutes, the solvent was carefully decanted from a viscous oil. ((/ V- (2- (sec-butyl) phenyl) carbamimidoyl) thio) methyl acetate HBr (B8), was dissolved in 8 ml of dry tetrahydrofuran and (4- (1- (4- (trifluorome- 4-nitrophenyl carbamate (3.26 g, 6.72 mmol) was added, followed by Hünig's base (2) phenyl) -1 / - / - 1,2,4-triazol-3-yl) phenyl) , 6 g, 20 mmol) The solution was allowed to stir at room temperature for 3 hours, then it was concentrated and the residue chromatographed (silica gel, 0-70% EtOAc-hexanes) to provide 730 mg (18%) of the title compound as a solid, melting point 169 at 177 ° C; 1H NMR (400 MHz, CDCh) δ 8.53 (s, 1H), 8.12 (d, J = 8.7 Hz, 2H), 7.81 - 7.74 (m, 2H), 7.63 - 7.56 (m, 2H), 7.52 (m, 1H), 7.45 (d , J = 7.9 Hz, 1H), 7.41 - 7.32 (m, 3H), 7.28 (s, 1H), 7.11 (d, J = 7.9 Hz, 1H), 4 , 03 - 3.95 (m, 2H), 2.43 (dd, J = 13.5, 6.8 Hz, 1H), 1.73 - 1.56 (m, 2H), 1.20 (overlap) d, J = 7.6 Hz, 3H), 0.78 (overlap t, J = 7.4 Hz, 3H); ESIMS m / z 594 ([M + H] +).
[00131] The following molecule was prepared according to the conditions described in the previous example. Example 19. Preparation of (Z) -1- (3- (2-isopropylphenyl) -4-oxothiazolidin-2-ylidene) -3- (4- (1 - (4- (trifluoromethoxy) phenyl) -1 H -1,2,4-triazol-3-yl) phenyl) urea (Molecule A19).

[00132] Of 0.70 g (2.0 mmol) of intermediate 2 - ((M- (2-isopropylphenyl) carbamimidoyl) thio) (E) -methyl acetate, HBr (B9) and 850 mg (1 , 75 mmol) of 4- (1- (4- (trifluoromethoxy) phenyl) -1 H-1,2,4-triazol-3-yl) phenyl) 4-nitrophenyl carbamate was obtained 320 mg (31 %) of the A19 molecule as a light brown solid, melting point 180 to 183 ° C; 1H NMR (CDCh) δ 8.53 (s, 1H), 8.12 (d, J = 8.7 Hz, 2H), 7.80 - 7.74 (m, 2H), 7.60 (d, J = 8.8 Hz, 2H), 7.54 - 7.45 (m, 2H), 7.40 - 7.34 (m, 3H), 7.32 (s, 1H), 7.10 (d , J = 7.5 Hz, 1H), 3.98 (d, J = 2.5 Hz, 2H), 2.73 (heptet, J = 6.9 Hz, 1H), 1.22 (dd, J = 6.8, 5.0 Hz, 6H); ESIMS m / z 581 ([M + H] +). Example 20. Preparation of (E) -3-hydroxy-2 - ((2-isopropylphenyl) carbamothioyl) -W- (4- (1 - (4- (trifluoromethoxy) phenyl) -1 H-1,2, 4-triazol-3-yl) phenyl) but-2-enamide (Molecule A20).

[00133] Step 1. A solution of 4- (1- (4- (trifluoromethoxy) phenyl) -1H- 1,2,4-triazol-3-yl) aniline (1.0 g, 3.12 mmol) and t-butyl acetoacetate (0.494 g, 3.12 mmol) in 8 ml of toluene was heated to 90 ° C for 2 hours, then cooled. The resulting solid was filtered and air dried to provide 1.12 g (89%) of 3-oxo- / V- (4- (1- (4- (trifluoromethoxy) phenyl) -1H-1,2, 4-triazol-3-yl) phenyl) -butanamide as a brown solid (B10); melting point 159 to 164 ° C. 1H NMR (CDCh) δ 9.35 (s, 1H), 8.55 (s, 1H), 8.19 - 8.09 (d, J = 8.7 Hz, 2H), 7.83 - 7, 74 (d, J = 9.1 Hz, 2H), 7.74 - 7.63 (d, J = 8.7 Hz, 2H), 7.43 - 7.32 (d, J = 8.3 Hz , 2H), 3.62 (s, 2H), 2.34 (s, 3H); 13C NMR (101 MHz, CDCh) δ 205.34, 163.43, 163.02, 148.34, 141.49, 138.84, 135.55, 127.37, 126.50, 122.37, 121 , 67, 121.16, 120.03, 49.56, 31.36; ESIMS m / z 581 ([M + HF).
[00134] Step 2. A portion of the solid from Step 1 (0.50 g, 1.24 mmol) was dissolved in 5 mL of dry / V, / V-dimethylformamide (DMF) and stirred at room temperature at the same time as potassium carbonate (0.25 g, 1.81 mmol) and 2-isopropylphenyl isothiocyanate (0.25 g, 1.41 mmol) were added. The solution was stirred for 18 hours, then it was poured into 15 ml of water, extracted with ether, and the solvent evaporated. Chromatography of the crude product (0-70% EtOAc-hexanes) gave 350 mg of the title compound as a not entirely white solid. Melting point 141 to 144 ° C. 1H NMR (400 MHz, CDCh) δ 15.35-14.58 (m, 1H), 10.93 (s, 1H), 8.57 (m, 3H), 8.31 - 8.11 (m, 6H), 7.71 (m, 12H), 7.56 - 7.30 (m, 15H), 5.35 (s, 1H), 3.02 (heptet, J = 6.9 Hz, 1H), 2.52 (s, 3H), 1.35 - 1.11 (m, 6H); ESIMS m / z 582 ([M + H] +.). Example 21. Preparation of 3 - ((2-isopropylphenyl) amino) -3-thioxo-N- (4- (1 - (4- (trifluoromethoxy) phenyl) -1 H-1,2,4-triazole-3- il) phenyl) propanamide (Molecule A21).

[00135] The A20 molecule (0.410 g, 0.71 mmol) was heated in 5 mL of MeOH for 90 minutes, then it was cooled, concentrated and chromatographed (0-70% EtOAc-hexanes) to provide 288 mg ( 75%) of the A21 molecule as a yellow solid, melting point 173 to 178 ° C. 1H NMR (CDCh) δ 10.46 (s, 1H), 8.57 (s, 1H), 8.38 (s, 1H), 8.19 (d, J = 8.7 Hz, 2H), 7 , 80 (d, J = 9.1 Hz, 2H), 7.67 (d, J = 8.8 Hz, 2H), 7.47 - 7.31 (m, 6H), 4.10 (s, 2H), 3.04 (heptet, J = 6.7 Hz, 1H), 1.22 (d, J = 6.9 Hz, 6H); ESIMS m / z 540 ([M + H] +).
[00136] The conditions described in Examples 20 and 21 were used to prepare the molecules in Examples 22 and 23. Example 22. Preparation of 3-thioxo-3- (o-tolylamino) -W- (4- (1- (4 - (trifluoromethoxy) phenyl) -1 H-1,2,4-triazol-3-yl) phenyl) propanamide (Molecule A22).

[00137] Using 2-methylphenyl isothiocyanate in place of 2-isopropylphenyl isothiocyanate in Step 2 of Example 20, 33 mg (52%) of Molecule A22 was obtained; 1H NMR (CDCh) δ 10.76 (s, 1H), 8.84 (s, 1H), 8.56 (s, 1H), 8.15-8.13 (d, J = 8.4 Hz, 2H), 7.81-7.74 (m, 3H), 7.66 - 7.33 (d, J = 8.4 Hz, 2H), 7.58 - 7.50 (m, 1H), 7 , 43 - 7.20 (m, 4H), 4.10 (s, 2H), 2.28 (s, 3H); ESIMS m / z 511 ([M + H] +). Example 23. Preparation of 3 - ((2,6-dimethylphenyl) amino) -3-thioxo-W- (4- (1 - (4- (trifluoromethoxy) phenyl) -1 H-1,2,4-triazole- 3-yl) phenyl) propanamide (Molecule A23).

[00138] Using 2,6-dimethylphenyl isothiocyanate in place of 2-isopropylphenyl isothiocyanate in Step 2 of Example 20, 185 mg (41%) of Molecule A23 was obtained as a light yellow solid, melting point 178 to 182 ° C; 1H NMR (CDCh) δ 10.41 (s, 1H), 8.88 (s, 1H), 8.58 (s, 1H), 8.15 (d, J = 8.7 Hz, 2H), 7 , 85 - 7.76 (m, 2H), 7.65 (d, J = 8.7 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.22 - 6, 99 (m, 3H), 4.14 (s, 2H), 2.22 (s, 6H); ESIMS m / z 526 ([M + H] +). Example 24. Preparation of (Z) -2- (3- (2-isopropylphenyl) -4-oxothiazolidin-2-ylidene) -W- (4- (1 - (4- (trifluoromethoxy) phenyl) -1 H -1,2,4-triazol-3-yl) phenyl) acetamide (Molecule A24).

[00139] The A21 molecule (0.031 g, 0.057 mmol) was dissolved in 4 ml of EtOH and treated with 20 mg (0.13 mmol) of methyl bromoacetate and 20 mg (0.24 mmol) of sodium acetate, and the solution was heated to reflux for 2 hours. The solution was then cooled, concentrated and chromatographed (0-70% EtOAc-hexanes) to provide 27 mg (73%) of the A24 molecule as a brown solid. Melting point> 250 ° C (dec). 1H NMR (CDCh) δ 8.53 (s, 1H), 8.13 - 8.07 (m, 2H), 7.81 - 7.76 (m, 2H), 7.61 (d, J = 8 , 6 Hz, 2H), 7.53 (d, J = 3.9 Hz, 2H), 7.42 - 7.33 (m, 2H), 7.23 - 7.16 (m, 1H), 7 , 13 (d, J = 7.7 Hz, 1H), 6.97 (s, 1H), 5.01 (s, 1H), 3.91 (s, 2H), 2.83-2.68 ( m, 1H), 1.31 - 1.16 (m, 6H); ESIMS m / z 580 ([M + H] +). Example 25. Preparation of (Z) -2-cyano-3 - ((2-isopropylphenyl) amino) - 3-mercapto-W- (4- (1 - (4- (trifluoromethoxy) phenyl) -1 H-1, 2,4-triazol-3-yl) phenyl) acrylamide (Molecule A25).

[00140] Step 1. Cyanoacetic acid (0.30 g, 3.53 mmol) and 4- (1- (4- (trifluoromethoxy) phenyl) -1H-1,2,4-triazol-3-yl) aniline ( 1.00 g, 3.12 mmol) were dissolved in 30 ml of dichloromethane, and then dicyclohexylcarbodiimide (0.695 g, 3.37 mmol) was added in one portion as a solid. The solution was allowed to stir for 2 hours, then the solvent was removed and the residue was heated in 75 ml of EtOAc, cooled and filtered to remove dicyclohexyl urea. The filtrate was concentrated and the solid was recrystallized from EtOH to provide 0.82 g (66%) of 2-cyano- / V- (4- (1- (4- (trifluoromethoxy) phenyl) -1H-1,2, 4-triazol-3-yl) phenyl) acetamide (B11) as a white solid, melting point 250 to 252 ° C. 1H NMR (DMSO-cfe) δ 10.51 (s, 1H), 9.39 (s, 1H), 8.13 - 8.00 (m, 4H), 7.75 - 7.66 (m, 2H ), 7.62 (d, J = 8.3 Hz, 2H), 3.95 (s, 2H). ESIMS m / z 388 (M + H).
[00141] Step 2. The cyanoacetanilide from Step 1 (0.30 g, 0.775 mmol) θ 2-isopropylphenyl isothiocyanate (0.16 g, 0.903 mmol) were dissolved in 5 ml_ of DMF and stirred under N2 at the same time that NaH (60%; 62 mg, 1.55 mmol) was added in one portion. The solution was allowed to stir at room temperature for 1 hour, then it was poured into 20 ml of 1 N HCI. The viscous solid was collected and crystallized from EtOH / water to provide 0.32 g (71%) of the title compound as a light yellow solid, melting point 159 to 162 ° C. 1H NMR (CDCh) δ 12.56 (s, 1H), 8.56 (s, 1H), 8.18 (d, J = 8.7 Hz, 2H), 7.85 - 7.77 (m, 2H), 7.68 - 7.60 (m, 3H), 7.45 - 7.36 (m, 4H), 7.32 - 7.27 (m, 1H), 7.20 (d, J = 7.7 Hz, 1H), 4.42 (s, 1H), 3.11 (liver, J = 6.9 Hz, 1H), 1.26 (d, J = 6.9 Hz, 6H) ; ESIMS m / z 565 ([M + H] +).
[00142] The following molecules (Examples 26-30) were prepared according to the procedure described in the previous Example. Example 26. (Z) -2-Cyano-3-mercapto-3 - (((4-methoxy-2-methylphenyl) amine) -W- (4- (1 - (4- (trifluoromethoxy) phenyl) -1 H-1,2,4-triazol-3-yl) phenyl) acrylamide (Molecule A26).

[00143] Molecule A26 was isolated as a light yellow solid, 103 mg (58%), melting point 174 to 177 ° C; 1H NMR (CDCh) δ 12.27 (s, 1H), 8.56 (s, 1H), 8.18 (d, J = 8.7 Hz, 2H), 7.80 (d, J = 9, 1 Hz, 2H), 7.63 (d, J = 8.9 Hz, 2H), 7.61 (s, 1H), 7.39 (d, J = 8.3 Hz, 2H), 7.12 (d, J = 8.6 Hz, 1H), 6.92 - 6.73 (m, 2H), 4.40 (s, 1H), 3.83 (s, 3H), 2.28 (s, 3H); ESIMS m / z 567 ([M + H] +). Example 27. (Z) -3 - ([1,1'-Biphenyl] -2-ylamino) -2-cyano-3-mercapto- / V- (4- (1 - (4- (trifluoromethoxy) phenyl) - 1 H-1,2,4-triazol-3-yl) phenyl) acrylamide (Molecule A27).

[00144] Molecule A27 was isolated as a light yellow solid, 60 mg (32%), melting point 162 to 166 ° C; 1H NMR (CDCh) δ 12.52 (s, 1H), 8.55 (s, 1H), 8.15 (d, J = 8.6 Hz, 2H), 7.80 (m, 3H), 7 , 57 - 7.28 (m, 13H), 4.29 (s, 1H); ESIMS m / z 599 ([M + H] +). Example 28. (Z) -2-Cyano-3-mercapto-3 - ((2,6-dimethylphenyl) amino) -W- (4. (1 - (4- (trifluoromethoxy) phenyl) -1 H-1, 2,4-triazol-3-yl) phenyl) acrylamide (Molecule A28).

[00145] Molecule A28 was isolated as a light yellow solid, 103 mg (59%), melting point 196 at 199 ° C; 1H NMR (CDCh) δ 12.24 (s, 1H), 8.56 (s, 1H), 8.18 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 9, 1 Hz, 2H), 7.64 (d, J = 8.7 Hz, 2H), 7.42 - 7.33 (m, 2H), 7.23 (m, 1H), 7.17 (d, J = 7.7 Hz, 2H), 4.30 (s, 1H), 2.28 (s, 6H); ESIMS m / z 551 ([M + H] +). Example 29. (Z) -2-Cyano-3-mercapto-3- (o-tolylamino) -W- (4- (1 - (4- (trifluoromethoxy) phenyl) -1H-1,2,4- triazol-3-yl) phenyl) acrylamide (Molecule A29).

[00146] Molecule A29 was isolated as a light yellow solid, 121 mg (71%), melting point 157 at 160 ° C; 1H NMR (CDCh) δ 12.51 (s, 1H), 8.56 (s, 1H), 8.18 (d, J = 8.8 Hz, 2H), 7.84 - 7.73 (m, 2H), 7.67 - 7.60 (m, 3H), 7.39 (d, J = 8.3 Hz, 2H), 7.32 (m, 3H), 7.23 (m, 1H), 4.42 (s, 1H), 2.33 (s, 3H); ESIMS m / z 537 ([M + H] +). Example 30. (Z) -2-Cyano-3 - ((2,6-difluorophenyl) amino) -3-mercapto-W- (4. (1 - (4- (trifluoromethoxy) phenyl) -1 H-1, 2,4-triazol-3-yl) phenyl) acrylamide (Molecule A30).

[00147] Molecule A30 was isolated as a light yellow solid, 53 mg (28%), melting point 135 to 142 ° C; 1H NMR (CDCh) δ 12.31 (s, 1H), 8.64 - 8.50 (m, 1H), 8.19 (dd, J = 13.9, 7.1 Hz, 2H), 7, 80 (m, 2H), 7.65 (m, 2H), 7.39 (m, 3H), 7.14 - 6.86 (m, 3H), 4.97 - 4.11 (m, 1H) ; ESIMS m / z 559 ([M + H] +). Example 31. (Z) -2-Cyano-2- (3- (2-isopropylphenyl) -4-oxothiazolidin-2 ylidene) -W- (4- (1 - (4- (trifluoromethoxy) phenyl) -1 H- 1,2,4-triazol-3-yl) phenyl) acetamide (Molecule A31).

[00148] The A25 molecule (0.058 g, 0.103 mmol) was dissolved in 3 mL of EtOH and treated with 35 mg (0.23 mmol) of methyl bromoacetate and 30 mg (0.37 mmol) of sodium acetate, and the solution was heated to reflux for 1 hour. The solution was then cooled and the solid product was filtered and air dried to provide 46 mg (71%) of thiazolinone as a light brown solid, melting point 250 to 255 ° C; 1H NMR (CDCh) δ 8.55 (s, 1H), 8.16 (d, J = 8.8 Hz, 2H), 7.95 (s, 1H), 7.79 (d, J = 9, 1 Hz, 2H), 7.62 (d, J = 8.8 Hz, 3H), 7.53 (dd, J = 7.8, 1.2 Hz, 1H), 7.42 - 7.34 ( m, 3H), 7.18 (dd, J = 7.9, 1.2 Hz, 1H), 3.92 (d, J = 1.3 Hz, 2H), 2.71 (heptide, J = 6 , 8 Hz, 1H), 1.33 (d, J = 6.9 Hz, 3H), 1.23 (d, J = 6.8 Hz, 3H); ESIMS m / z 605 ([M + HD- Example 32. Preparation of (Z) -3- (2,6-dimethylphenylamino) -3-hydroxy- 1- (4- (1 - (4- (trifluoromethoxy) phenyl) -1 H-1,2,4-triazol-3-yl) phenyl) acrylamide (Molecule A32).

[00149] Step 1. To a stirred solution of 4- (1- (4- (trifluoromethoxy) phenyl) -1 H-1,2,4-triazol-3-yl) aniline (0.19 g; 0.593 mmol) and mono-benzyl malonic acid (0.138 g, 0.712 mmol) dissolved in DMF (6 ml_) 1-hydroxy-7-azabenzotriazole (HOAt, 0.5 M in DMF; 2.14 ml_; 1.068 mmol) was added, followed by 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDCI; 0.21 g; 1.068 mmol) and / V-methyl morpholine (0.46 ml; 4.15 mmol). The mixture was stirred overnight. Water (25 ml) was then added and the solution was extracted with EtOAc (3x10 ml). The organic solution was washed with water (5x10 ml) and brine (10 ml), followed by drying over MgSO4, filtration and concentration. The residue was applied to 1 g of Isolute SCX-2 column and eluted with a 9: 1 CHCh / MeOH solution to provide the expected amide (B12), contaminated with about 10% dimethyl amide or oxo-propanoic acid from the beginning ( 0.26 g; 88%). 1H NMR (CDCh) δ 9.35 (s, 1H), 8.55 (s, 1H), 8.15 (d, J = 8.7 Hz, 2H), 7.78 (d, J = 9, 0 Hz, 2H), 7.67 (d, J = 8.7 Hz, 2H), 7.35 (m, 7H), 5.23 (s, 2H), 3.54 (s, 2H). 13C NMR (101 MHz, CDCh) δ 169.59, 167.45, 162.84, 141.53, 138.91, 135.58, 134.81, 128.77, 128.60, 128.52, 128 , 41, 128.36, 127.37, 122.39, 121.17, 119.97, 67.65, 41.76, 35.58. ESIMS m / z 496 ([M + H] +)
[00150] Step 2. The benzyl ester from Step 1 (0.26 g; 0.524 mmol) was dissolved in 4 mL of MeOH and eluted through the H-Cuba hydrogenator at 50 ° C (1 mL / minute) using 10% Pd / C cartridge as the catalyst. The MeOH was concentrated and the crude acid was dried under high vacuum overnight. The acid (B13) (0.162 g; 76%) was used directly in the next Step 1H NMR (DMSO-dθ) δ 10.35 (s, 1H), 9.38 (s, 1H), 8.06 (dd, J = 8.9, 3.3 Hz, 4H), 7.74 (d, J = 8.8 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.37 ( s, 1H), 3.39 (s, 2H). ESIMS m / z 406 ([M + H] +)
[00151] Step 3. To a solution of the carboxylic acid from Step 2 (62 mg; 0.153 mmol) and 2,6-dimethyl aniline (20 µL; 0.153 mmol) in DMF (1.6 mL) was added HOAt (0, 5 M in DMF; 0.55 ml; 0.275 mmol), EDCI HCI (53 mg; 0.275 mmol) and A / -methyl morpholine (0.18 ml; 1.068 mmol). The reaction was stirred at room temperature overnight. The solution was diluted with water and extracted with EtOAc. The organic solution was washed with water (5x) and brine. The solution was then dried over MgSO4, filtered and concentrated. The residue was purified by means of radial chromatography using a 97.5: 2.5 ratio of CHCh / MeOH as the eluent (Rf = 0.2). The product containing fraction was contaminated with the carboxylic acid dimethyl amide from the beginning. This mixture was purified by means of reverse phase chromatography using the CH3CN / H2O gradient to provide the pure desired diameter (9 mg; 12%). 1H NMR (CDCh; mix of resonance forms, highest reported) δ 10.53 (s, 1H), 9.71 (s, 1H), 8.55 (s, 1H), 8.13 (m, 3H) , 7.79 (d, J = 9.1 Hz, 2H), 7.71 (d, J = 8.7 Hz, 1H), 7.65 (d, J = 8.7 Hz, 1H), 7 , 37 (d, J = 8.3 Hz, 2H), 7.12 (m, 1H), 3.49 (s, 2H), 3.12 (s, 3H), 3.04 (s, 3H) . ESIMS m / z 509 ([M + H] +) Example 33. Preparation of (Z) -3-hydroxy-3- (4-methoxy-2-methylphenyl-mino) -W- (4- (1 - (4 - (trifluoromethoxy) phenyl) -1 H-1,2,4-triazol-3-ll) phenyl) acrylamide (Molecule A33).

[00152] Using Step 3 of the above procedure, and replacing 2,6-dimethylaniline with 2-methyl-4-methoxyaniline, 83 mg (56%) of the diamide was obtained as a brown solid, melting point 168 to 171 ° C. 1H NMR (DMSO-dθ) δ 10.39 (s, 1H), 9.48 (s, 1H), 9.38 (s, 1H), 8.07 (d, J = 8.9 Hz, 4H) , 7.77 (d, J = 8.8 Hz, 2H), 7.62 (d, J = 8.3 Hz, 2H), 7.28 (d, J = 8.7 Hz, 1H), 6 , 81 (d, J = 2.8 Hz, 1H), 6.74 (dd, J = 8.7, 2.9 Hz, 1H), 3.73 (s, 3H), 3.51 (s, 2H), 2.21 (s, 3H). EIMS 525 (M +). Example 34. Preparation of (Z) -3-hydroxy-3- (2-isopropyl-4-methoxyphenylamino) -H- (4- (1 - (4- (trifluoromethoxy) phenyl) -1 H-1,2, 4-triazol-3-yl) phenyl) acrylamide (Molecule A34).

[00153] Using Step 3 of the above procedure, and replacing 2,6-dimethylaniline with 2-isopropyl-4-methoxyaniline, 38 mg (36%) of the diamide was obtained. 1H NMR (CDCh) δ 9.81 (s, 1H), 8.92 (s, 1H), 8.58 (s, 1H), 8.12 (d, J = 8.6 Hz, 2H), 7 , 79 (d, J = 9.0 Hz, 2H), 7.69 (d, J = 8.7 Hz, 2H), 7.50 - 7.10 (m, 3H), 6.84 (d, J = 2.8 Hz, 1H), 6.72 (dd, J = 8.7, 2.9 Hz, 1H), 4.02 (s, 3H), 3.80 (s, 2H), 3, 08 (dt, J = 13.6, 6.8 Hz, 1H), 1.20 (d, J = 6.9 Hz, 6H). 13C NMR (101 MHz, CDCh) δ 166.81, 166.13, 162.98, 158.40, 144.30, 141.54, 139.02, 135.54, 127.30, 127.05, 126 , 87, 126.52, 126.30, 122.36, 121.13, 120.10, 111.97, 110.85, 56.04, 55.36, 44.26, 28.37, 23.06 . ESIMS m / z 553 ([M + H] +) Example 35. Preparation of 4-fluorine-2-nitro-1- (prope-1-en-2-yl) benzene (B14)

[00154] 1-chloro-4-fluoro-2-nitrobenzene (1.03 g, 5.87 mmol) in a 100 ml circular base flask equipped with a stir bar and nitrogen was added sodium carbonate (0.746 g , 7.04 mmol), dioxane (23.47 mL) and water (5.87 mL). To this was added 4,4,5,5-tetramethyl-2- (prope-1-en-2-yl) -1,3,2-dioxaborolane (1,323 ml, 7.04 mmol) followed by bis (triphenylphosphine) palladium (ll) chloride (0.329 g, 0.469 mmol). The reaction mixture was evacuated and charged again with nitrogen (3x). The reaction was heated to 80 ° C overnight. The reaction was determined to be complete by TLC (10% EtOAc / Hex). The reaction was cooled, filtered through Celite, washed with EtOAc and concentrated. The residue was taken up in dichloromethane, poured through a phase separator and concentrated. Purification by flash column chromatography gave the title compound 4-fluorine-2-nitro-1- (prope-1-en-2-yl) benzene (0.837 g, 75%) as a yellow oil: IR (thin film) 3091 (w), 2979 (w), 2918 (w), 1642 (w), 1530 (s), 1350 (s) cm * 1; 1H NMR (400 MHz, CDCh) δ 7.60 (dd, J = 8.2, 2.5 Hz, 1H), 7.37 - 7.21 (m, 2H), 5.19 (p, J = 1.5 Hz, 1H), 4.97 - 4.89 (m, 1H), 2.11 - 2.04 (m, 3H); 13C NMR (101 MHz, CDCh) δ 160.96 (d, JCF = 250.8 Hz), 148.46,141.88, 135.18 (d, JCF = 4.1 Hz), 132.09 (d, J CF = 7.8 Hz), 119.98 (d, JCF = 20.9 Hz), 115.99, 111.63 (d, JCF = 26.4 Hz), 23.35.
[00155] The following molecules (B15 and B16) were made according to the procedures described in example 35. 1-Fluorine-3-nitro-2- (prope-1-en-2-yl) benzene (B15)

[00156] IR (thin film) 3091 (w), 2978 (w), 2922 (w), 1645 (w), 1528 (s), 1355 (s) cm1; 1H NMR (400 MHz, CDCh) δ 7.64 (dt, J = 8.1, 1.2 Hz, 1H), 7.39 (td, J = 8.2, 5.4 Hz, 1H), 7 , 31 (td, J = 8.5, 1.2 Hz, 1H), 5.28 (p, J = 1.5 Hz, 1H), 4.91 (p, J = 1.0 Hz, 1H) , 2.16 (t, J = 1.3 Hz, 3H); 13C NMR (101 MHz, CDCh) δ 159.59 (d, JCF = 249.3 Hz), 149.81, 136.14, 128.57 (d, JCF = 9.0 Hz), 127.02 (d , JCF = 22.0 Hz), 119.84 (d, JCF = 23.4 Hz), 119.41 (d, JCF = 3.6 Hz), 117.25, 23.10 (d, JCF = 1 , 9 Hz). 4-Fluoro-nitro-2- (prope-1-en-2-yl) benzene (B16)

[00157] IR (thin film) 3085 (w), 2979 (w), 2919 (w), 1617 (m), 1580 (s), 1523 (s), 1344 (s) cm -1; 1H NMR (400 MHz, CDCh) δ 7.96 (dd, J = 9.0, 5.1 Hz, 1H), 7.08 (ddd, J = 9.0, 7.4, 2.8 Hz, 1H), 7.02 (dd, J = 8.7, 2.8 Hz, 1H), 5.20 (p, J = 1.5 Hz, 1H), 4.96 (p, J = 1.0 Hz, 1H), 2.11 -2.06 (m, 3H). Example 36. Preparation of 5-fluorine-2-isopropylaniline (B17)

[00158] 4-fluorine-2-nitro-1- (prope-1-en-2-yl) benzene (0.837 g, 4.62 mmol) in a 250 ml circular base flask equipped with a stir bar and rubber septum was added EtOAc (46.2 ml) followed by palladium on carbon (0.983 g, 0.462 mmol). The reaction was evacuated and purged with hydrogen (flask) (2x) and stirred under hydrogen at room temperature overnight. The reaction was determined to be complete by TLC (10% EtOAc / Hex). The mixture was filtered through Celite, washed with EtOAc and concentrated. 5-Fluorine-2-isopropylaniline (673 mg, 4.40 mmol, 95%) was obtained as a clear yellow oil: IR (thin film) 3480 (w), 3390 (w), 2962 (m), 2872 ( w), 1622 (m), 1504 (s), 1431 (m) cm -1; 1H NMR (400 MHz, CDCh) δ 7.05 (dd, J = 8.5, 6.4 Hz, 1H), 6.45 (td, J = 8.5, 2.6 Hz, 1H), 6 , 37 (dd, J = 10.6, 2.6 Hz, 1H), 3.74 (bs, 2H), 2.83 (hept, J = 6.8 Hz, 1H), 1.24 (d, J = 6.8 Hz, 6H); 13C NMR (101 MHz, CDCh) δ 161.75 (d, JCF = 241.3 Hz), 144.76 (d, JCF = 10.3 Hz), 128.11 (d, JCF = 2.8 Hz) , 126.53 (d, JCF = 9.6 Hz), 105.06 (d, JCF = 20.7 Hz), 102.26 (d, JCF = 24.2 Hz), 27.27, 22.35 .
[00159] The following molecules were made according to the procedures described in example 36. 3-Fluorine-2-isopropylaniline (B18)

[00160] IR (thin film) 3478 (w), 3386 (w), 2963 (m), 2934 (w), 2934 (w), 1624 (s), 1466 (s), 1453 (s) cm1; 1H NMR (400 MHz, CDCh) δ 6.92 (td, J = 8.1, 6.1 Hz, 1H), 6.44 (ddd, J = 10.4, 8.1, 1.1 Hz, 2H), 3.72 (bs, 2H), 3.06 (heptd, J = 7.1, 1.3 Hz, 1H), 1.35 (dd, J = 7.1, 1.5 Hz, 6H ); 13C NMR (101 MHz, CDCh) δ 162.83 (d, JCF = 243.4 Hz), 145.29 (d, JCF = 8.8 Hz), 127.08 (d, JCF = 11.2 Hz) , 119.64 (d, JCF = 16.1 Hz), 111.77 (d, JCF = 2.3 Hz), 106.47 (d, JCF = 24.2 Hz), 25.65, 20.97 (d, J cr = 3.8 Hz). 4-Fluorine-2-isopropylaniline (B19)

[00161] IR (thin film) 3455 (w), 3373 (w), 2962 (m), 2870 (w), 1625 (w), 1609 (w), 1497 (s), 1429 (m) cm1; 1H NMR (400 MHz, CDCh) δ 6.85 (dd, J = 10.3, 2.9 Hz, 1H), 6.72 (td, J = 8.3, 2.9 Hz, 1H), 6 , 60 (dd, J = 8.6, 5.1 Hz, 1H), 3.49 (bs, 2H), 2.88 (hept, J = 6.8 1H), 1.24 (d, J = 6.8 Hz, 6H); 13C NMR (101 MHz, CDCh) δ 156.92 (d, JCF = 235.0 Hz), 139.17 (d, JCF = 2.1 Hz), 134.61 (d, JCF = 6.2 Hz) , 116.55 (d, JCF = 7.5 Hz), 112.69 (d, JCF = 22.5 Hz), 112.17 (d, JCF = 22.4 Hz), 27.90,22.11 . Example 37. Preparation of / V - ((2-cyclopropylphenyl) carbamoylthio) benzamide (B20)

[00162] 2-Cyclopropylaniline (498 mg, 3.74 mmol) in acetone (10 mL) was added benzoyl isothiocyanate (0.53 mL, 3.93 mmol) and the mixture was heated at 50 ° C for 8 hours . The reaction mixture was concentrated to provide A / - ((2-cyclopropylphenyl) carbamothioyl) benzamide as an orange oil (1.249 g, 100%): 1H NMR (400 MHz, CDCh) δ 12.59 (s, 1H) , 9.14 (s, 1H), 8.07 (dd, J = 7.8, 1.3 Hz, 1H), 7.92 (dd, J = 8.4, 1.2 Hz, 2H), 7.69 - 7.63 (m, 1H), 7.59 - 7.52 (m, 2H), 7.31-7.26 (m, 1H), 7.23 (td, J = 7.5 , 1.5 Hz, 1H), 7.13 (dd, J = 7.6, 1.5 Hz, 1H), 1.95 (qt, J = 12.3, 4.4 Hz, 1H), 1 , 09-1.01 (m, 2H), 0.76 - 0.69 (m, 2H); 13C NMR (101 MHz, CDCh) δ 178.70, 166.72, 137.59, 137.06, 133.71, 131.72, 129.22, 127.51, 127.20, 126.93, 126 , 12, 125.26, 11.72, 7.03; ESIMS m / z 295 ([M-H] ').
[00163] The following molecules were made according to the procedures described in example 37. N - ((2-chloro-6-isopropylphenyl) carbamothioyl) benzamide (B21)

[00164] mp 177-181 ° C; 1H NMR (400 MHz, CDCh) δ 11.92 (s, 1H), 9.25 (s, 1H), 7.98 - 7.89 (m, 2H), 7.72 - 7.62 (m, 1H), 7.62 - 7.51 (m, 2H), 7.40 - 7.28 (m, 3H), 3.17 (hept, J = 6.9 Hz, 1H), 1.33 (d , J = 6.8 Hz, 3H), 1.21 (d, J = 6.9 Hz, 3H); ESIMS m / z 333 ([M + H] +). N - (((5-fluoro-2-isopropylphenyl) carbamothioyl) benzamide (B22)

[00165] mp 134 ° C (dec.); 1H NMR (400 MHz, CDCh) δ 12.31 (s, 1H), 9.17 (s, 1H), 7.96 - 7.87 (m, 2H), 7.73 - 7.62 (m, 1H), 7.61 - 7.49 (m, 3H), 7.33 (dd, J = 8.8, 6.1 Hz, 1H), 7.03 (td, J = 8.3, 2, 8 Hz, 1H), 3.13 (hept, J = 6.9 Hz, 1H), 1.27 (d, J = 7.0 Hz, 6H); ESIMS m / z 315 ([MH] ') ■ N - ((2-isopropyl-5-methylphenyl) carbamothioyl) benzamide (B23)

[00166] 1H NMR (400 MHz, CDCh) δ 12.14 (s, 1H), 9.18 (s, 1H), 7.97 - 7.87 (m, 2H), 7.73 - 7.61 (m, 1H), 7.61 - 7.50 (m, 2H), 7.42 - 7.34 (m, 1H), 7.31 - 7.23 (m, 1H), 7.16 (dd , J = 7.9, 1.8 Hz, 1H), 3.11 (hept, J = 6.9 Hz, 1H), 2.36 (s, 3H), 1.26 (d, J = 6, 9 Hz, 6H); 13C NMR (101 MHz, CDCh) δ 180.23, 166.97, 140.94, 136.03, 134.89, 133.75, 131.67, 129.22, 129.20, 127.71, 127 , 55, 126.01, 28.17, 23.38, 20.90; ESIMS m / z 311 ([MH] "). / V - ((2-isopropyl-4-methylphenyl) carbamothioyl) benzamide (B24)

[00167] mp 136 ° C (dec.); 1H NMR (400 MHz, CDCh) δ 12.11 (s, 1H), 9.17 (s, 1H), 7.97 - 7.86 (m, 2H), 7.72 - 7.61 (m, 1H), 7.60 - 7.49 (m, 2H), 7.44 (d, J = 8.0 Hz, 1H), 7.18 (d, J = 1.9 Hz, 1H), 7, 09 (dd, J = 8.1, 2.0 Hz, 1H), 3.11 (hept, J = 6.8 Hz, 1H), 2.38 (s, 3H), 1.27 (d, J = 6.9 Hz, 6H); ESIMS m / z 311 ([MH]). A / - (((2-isopropyl-3-methylphenyl) carbamothioyl) benzamide (B25)

[00168] 1H NMR (400 MHz, CDCh) δ 12.12 (s, 1H), 9.18 (s, 1H), 7.99 - 7.86 (m, 2H), 7.71 - 7.60 (m, 1H), 7.60 - 7.50 (m, 2H), 7.32 (dd, J = 6.6, 2.8 Hz, 1H), 7.21 - 7.09 (m, 2H ), 3.46 - 3.31 (m, 1H), 2.42 (s, 3H), 1.37 (d, J = 7.2 Hz, 6H); 13C NMR (101 MHz, CDCh) δ 180.41, 166.88, 141.79, 137.22, 136.15, 133.76, 131.65, 130.94, 130.53, 129.23, 127 , 57, 126.02, 28.69, 21.17, 21.05; ESIMS m / z 311 ([MH]). N - (((3-fluoro-2-isopropylphenyl) carbamothioyl) benzamide (B26)

[00169] 1H NMR (400 MHz, CDCh) δ 12.11 (s, 1H), 9.20 (s, 1H), 8.00 - 7.85 (m, 2H), 7.73 - 7.62 (m, 1H), 7.62 - 7.50 (m, 2H), 7.32 - 7.18 (m, 2H), 7.11 -6.98 (m, 1H), 3.27-3 , 14 (m, 1H), 1.38 (dd, J = 7.1, 1.4 Hz, 6H); 13C NMR (101 MHz, CDCh) δ 180.87, 167.04, 162.36 (d, JCF = 247.2 Hz), 136.61 (d, JCF = 8.8 Hz), 133.88, 132 , 02 (d, JCF = 15.2 Hz), 131.50,129,27,127,57,127,06 (d, JCF = 10,2 Hz), 123,77 (d, JCF = 3,0 Hz), 116,04 (d, JCF = 23.5 Hz), 27.36, 21.35, 21.31; ESIMS m / z 315 ([MH] '). N - (((4-fluoro-2-isopropylphenyl) carbamothioyl) benzamide (B27)

[00170] mp 96-102 ° C; 1H NMR (400 MHz, CDCl3) δ 12.11 (s, 1H), 9.18 (s, 1H), 7.97 - 7.87 (m, 2H), 7.73 - 7.63 (m, 1H), 7.60 - 7.48 (m, 3H), 7.07 (dd, J = 10.0, 2.9 Hz, 1H), 6.97 (ddd, J = 8.7, 7, 7, 2.9 Hz, 1H), 3.20 - 3.06 (m, 1H), 1.27 (d, J = 6.8 Hz, 6H); ESIMS m / z 315 ([M-H] -). N - (((1-isopropyl-1 H-pyrazol-5-yl) carbamothioyl) benzamide (B28)

[00171] 1H NMR (400 MHz, CDCh) δ 12.37 (s, 1H), 9.24 (s, 1H), 7.97 - 7.85 (m, 2H), 7.75 - 7.63 (m, 1H), 7.58 (ddd, J = 7.6, 5.9, 2.4 Hz, 3H), 6.56 (d, J = 1.9 Hz, 1H), 4.49 ( hept, J = 6.6 Hz, 1H), 1.54 (d, J = 6.7 Hz, 6H); 13C NMR (101 MHz, CDCh) δ 179.82, 167.18, 138.45, 134.40, 134.13, 131.16, 129.37, 127.58, 101.12, 49.79.22 , 33; ESIMS m / z 289 ([M + H] +). A / - ((3-isopropylphenyl) carbamothioyl) benzamide (B29)

[00172] 1H NMR (400 MHz, CDCh) δ 12.57 (s, 1H), 9.05 (s, 1H), 7.96 - 7.84 (m, 2H), 7.72 - 7.49 (m, 5H), 7.35 (t, J = 7.8 Hz, 1H), 7.15 (dt, J = 7.7, 1.3 Hz, 1H), 2.95 (hept, J = 6.9 Hz, 1H), 1.28 (d, J = 6.9 Hz, 6H); 13C NMR (101 MHz, CDCh) δ 178.05, 166.86, 149.90, 137.52, 133.75, 131.70, 129.25, 128.73, 127.46, 125.11, 122 , 10, 121.43, 34.04, 23.87; ESIMS m / z 299 ([M + H] +). Example 38. Preparation of 1- (2-cyclopropylphenyl) thiourea (B30)

[00173] A / V - ((2-cyclopropylphenyl) carbamothioyl) benzamide (1.210 g, 4.08 mmol) in MeOH (10 mL) was added 2 N NaOH (4.1 mL, 8.17 mmol) and stirred at 65 ° C for 3 hours. The reaction was cooled, neutralized with 2 N HCI, and half the reaction volume was evaporated under a stream of nitrogen. A yellow precipitate formed, which was filtered, rinsed with water and dried in a vacuum oven to provide 1- (2-cyclopropylphenyl) thiourea as a yellow solid (444.5 mg, 56%): melting point 152 to 154 ° C; 1H NMR (400 MHz, CDCh) δ 7.75 (s, 1H), 7.31 - 7.27 (m, 1H), 7.26 - 7.22 (m, 2H), 7.00 (d, J = 7.4 Hz, 1H), 5.95 (s, 2H), 1.99 (tt, J = 8.4, 5.3 Hz, 1H), 1.06 (ddd, J = 8.4 , 6.3, 4.5 Hz, 2H), 0.69 (dt, J = 6.4, 4.6 Hz, 2H); 13C NMR (101 MHz, CDCh) δ 182.10, 140.33, 135.18, 128.81, 126.96, 126.45, 126.04, 10.95, 8.39; ESIMS m / z 193 ([M + H] +).
[00174] The following molecules were made according to the procedures described in example 38. 1 - (2-Chloro-6-isopropylphenyl) thiourea (B31)

[00175] 1H NMR (400 MHz, CDCh) δ 7.63 - 7.52 (m, 1H), 7.40 - 7.29 (m, 3H), 5.30 (bs, 2H), 3.24 (hept, J = 6.9 Hz, 1H), 1.34-1.11 (m, 6H); 13C NMR (101 MHz, CDCh) δ 182.68, 149.91, 133.87, 130.66, 130.41, 128.07, 125.63, 29.11, 24.11; ESIMS m / z 227 ([MH]). 1 - (5-Fluorine-2-isopropylphenyl) thiourea (B32)

[00176] 1H NMR (400 MHz, CDCh) δ 7.89 (s, 1H), 7.37 (dd, J = 8.8, 6.1 Hz, 1H), 7.13 - 7.05 (m , 1H), 6.97 (dd, J = 8.8, 2.7 Hz, 1H), 5.98 (s, 2H), 3.16 (hept, J = 6.9 Hz, 1H), 1 , 21 (d, J = 6.9 Hz, 6H); 19F NMR (376 MHz, CDCh) δ -114.00; ESIMS m / z 211 ([MH]). 1 - (2-lsopropyl-5-methylphenyl) thiourea (B33)

[00177] 1H NMR (400 MHz, CDCh) δ 7.58 (s, 1H), 7.29 (d, J = 8.0 Hz, 1H), 7.18 (dd, J = 8.1, 1 , 9 Hz, 1H), 7.05 - 6.99 (m, 1H), 6.33 - 5.36 (m, 2H), 3.13 (hept, J = 6.9 Hz, 1H), 2 , 45 - 2.23 (m, 3H), 1.29 - 1.10 (m, 6H); 13C NMR (101 MHz, CDCh) δ 182.36, 143.05, 137.35, 132.92, 130.29, 127.99, 127.20, 27.94, 23.54, 20.74; ESIMS m / z 207 ([MH]). 1 - (2-lsopropyl-4-methylphenyl) thiourea (B34)

[00178] 1H NMR (400 MHz, CDCh) δ 7.64 - 7.51 (m, 1H), 7.21 - 7.17 (m, 1H), 7.13 - 7.02 (m, 2H) , 6.35 - 5.31 (m, 2H), 3.14 (hept, J = 6.9 Hz, 1H), 2.37 (s, 3H), 1.21 (d, J = 6.9 Hz, 6H); 13C NMR (101 MHz, CDCh) δ 182.50, 146.05, 139.59, 130.49, 128.03, 127.94, 127.52, 28.18, 23.49, 21.37; ESIMS m / z 207 ([MH]). 1 - (2-lsopropyl-3-methylphenyl) thiourea (B35)

[00179] 1H NMR (400 MHz, CDCh) δ 7.52 (d, J = 4.2 Hz, 1H), 7.20 - 7.12 (m, 2H), 7.05 (dd, J = 6 , 6, 2.7 Hz, 1H), 6.34 - 5.05 (m, 2H), 3.40 (hept, J = 7.3 Hz, 1H), 2.41 (s, 3H), 1 , 33 (d, J = 7.2 Hz, 6H); 13C NMR (101 MHz, CDCh) δ 182.09, 143.68, 138.60, 134.25, 131.94, 127.11, 126.66, 28.66, 21.00, 20.92; ESIMS m / z 209 ([M + H] +). 1 - (3-Fluorine-2-isopropylphenyl) thiourea (B36)

[00180] 1H NMR (400 MHz, CDCh) δ 7.74 - 7.56 (m, 1H), 7.32 - 7.19 (m, 1H), 7.13 - 7.01 (m, 2H) , 6.41 - 5.27 (m, 2H), 3.35 - 3.17 (m, 1H), 1.33 (dd, J = 7.1, 1.3 Hz, 6H); 19F NMR (376 MHz, CDCh) δ - 110.45; ESIMS m / z 211 ([MH] +). 1 - (4-Fluorine-2-isopropylphenyl) thiourea (B37)

[00181] 1H NMR (400 MHz, CDCh) δ 7.59 - 7.42 (m, 1H), 7.25 - 7.18 (m, 1H), 7.12 - 7.05 (m, 1H) , 7.02 - 6.91 (m, 1H), 6.33 - 5.27 (m, 2H), 3.24 - 3.08 (m, 1H), 1.22 (d, J = 6, 8 Hz, 6H); 19F NMR (376 MHz, CDCh) δ-110.29; ESIMS m / z 211 ([MH]). 1 - (1-lsopropyl-1 H-pyrazol-5-yl) thiourea (B38)

[00182] 1H NMR (400 MHz, DMSO-cfe) δ 9.35 (s, 1H), 8.07 (s, 1H), 7.41 (d, J = 1.9 Hz, 1H), 7, 10 (s, 1H), 6.07 (d, J = 1.9 Hz, 1H), 4.36 (hept, J = 6.6 Hz, 1H), 1.33 (d, J = 6.6 Hz, 6H); 13C NMR (101 MHz, DMSO-dβ) δ 183.02, 137.47, 135.00, 102.00.48,12,22,27; ESIMS m / z 185 ([M + H] +). 1 - (3-lsopropylphenyl) thiourea (B39)

[00183] 1H NMR (400 MHz, CDCh) δ 7.99 (s, 1H), 7.36 (t, J = 7.8 Hz, 1H), 7.20 (dt, J = 7.8, 1 , 4 Hz, 1H), 7.12-7.02 (m, 2H), 6.11 (s, 2H), 2.92 (hept, J = 6.9 Hz, 1H), 1.25 (d , J = 7.0 Hz, 6H); 13C NMR (101 MHz, CDCh) δ 181.65, 151.61, 136.18, 130.11, 126.13, 123.17, 122.40, 33.98, 23.83; ESIMS m / z 195 ([M + H] +). Example 39. Preparation of W - [[(2-isopropylphenyl) amino] thioxomethyl] - W '- (4- (1 - (4- (trifluoromethyl) phenyl) -1 H-1,2,4-triazole-3- il) phenyl urea. (A-molecule A48)

[00184] 4- (1- (4- (trifluoromethoxy) phenyl) -1 / - / - 1,2,4-triazol-3-yl) benzoyl azide (300 mg, 0.802 mmol). The flask was evacuated / refilled with N2, then toluene (20.0 ml) was added, followed by 1- (2-isopropylphenyl) thiourea (30 mg, 0.154 mmol). The reaction mixture was heated at 100 ° C for 1 hour. The reaction was then cooled to 50 ° C and stirred for an additional 1 h. The reaction mixture was then cooled to 35 ° C. THF (1 ml) was added, followed by sodium hydride (32.1 mg, 0.802 mmol) in one portion. Vigorous bubbling occurred and the reaction mixture turned yellow. The reaction mixture was stirred at 35 ° C for an additional 15 minutes. The reaction mixture was cooled to room temperature, poured over ice water, extracted with Et2O, dried, and concentrated on silica. The crude residue was purified by means of flash chromatography (silica / EtOAc / hexanes) to produce the title compound as a white solid (57 mg, 0.104 mmol, 13%): melting point 201 at 203 ° C; 1H NMR (400 MHz, CDCh) δ 8.57 (s, 1H), 8.16 (m, 2H), 7.80 (m, 3H), 7.56 (d, J = 8.3 Hz, 2H ), 7.40 (ddt, J = 8.0, 6.7, 1.7 Hz, 2H), 7.28 (dt, J = 6.8, 1.8 Hz, 2H), 7.23 ( m, 2H), 3.16 (sd, J = 16.4, 6.9 Hz, 3H), 1.22 (d, J = 6.9 Hz, 6H); 19F NMR (376 MHz, CDCh) δ -58.02; EIMS m / z 542 ([M + 2]).
[00185] The molecules A46, A63, A64, A67, A68, A70-A73, A78-A84, A89, A97-A101, A106, A107, A112, A113, A116, A118 and A119 in Table 1 were made according to the procedures described in Example 39 or by the procedure described in Example 53. Example 41. Preparation of W - [[(2-methyl-4-methoxyphenyl) amino] oxo-methyl] -Af- (4- (1 - (4- (trifluoromethyl) phenyl) -1 H-1,2,4-triazol-3-yl) phenyl urea (Molecule A53).

[00186] In a 100 ml circular base flask 1- (4- (1- (4- (trifluoromethoxy) phenyl) -1H-1,2,4-triazol-3-yl) phenyl) urea (200 mg, 0.551 mmol) and 1-isocyanate-4-methoxy-2-methylbenzene (135 mg, 0.826 mmol) in dioxane (10 mL). The vessel was heated to 100 ° C for 2 hours before the contents were cooled and the solvent removed under reduced pressure. The residue was suspended in DCM and purified by normal phase chromatography (silica gel; hexanes / EtOAc) to provide the title product as a white solid (30 mg): melting point 213-233 ° C; 1H NMR (400 MHz, DMSO-dθ) δ 10.71 (s, 1H), 10.34 (s, 1H), 10.13 (s, 1H), 9.39 (s, 1H), 8.08 (m, 4H), 7.70 - 7.57 (m, 4H), 7.26 (d, J = 8.7 Hz, 1H), 6.87 (d, J = 2.9 Hz, 1H) , 6.81 (dd, J = 8.7, 2.9 Hz, 1H), 3.75 (s, 3H), 2.20 (s, 3H); EIMS m / z 527 ([M + H] +). Example 42. Preparation of (E) -methyl 4- (3- (dimethylamino) acryloyl) benzoate (B40)

[00187] A mixture of methyl 4-acetylbenzoate (5.00 g, 28.1 mmol) in DMF-DMA (38 mL, 284 mmol) was heated to 105 ° C for 20 hours. The reaction was cooled, concentrated, and used raw in the next reaction. Example 43. Preparation of methyl 4- (1H-pyrazol-3-yl) benzoate (B41)

[00188] To a solution of crude (E) -methyl 4- (3- (dimethylamino) acryloyl) benzoate (28.1 mmol) in EtOH (100 mL) was added hydrazine monohydrate (1.50 mL, 30 , 9 mmol) and the reaction was heated to 50 ° C for 24 hours. The reaction temperature was then raised to 60 ° C for 24 hours. Additional hydrazine monohydrate (1.5 ml) was added, and the reaction was heated to 60 ° C for an additional 6 hours. The reaction was cooled, concentrated, and dried in a vacuum oven at 45 ° C overnight to produce methyl 4- (1H-pyrazol-3-yl) benzoate as an orange solid (8.15 g, quantitative) : melting point 106 ° C (dec); 1H NMR (400 MHz, CDCh) δ 8.15 - 8.05 (m, 2H), 7.91 - 7.83 (m, 2H), 7.65 (d, J = 2.4 Hz, 1H) , 6.71 (d, J = 2.3 Hz, 1H), 3.94 (s, 3H); 13C NMR (101 MHz, CDCh) δ 166.91, 136.89, 131.83, 130.13, 129.37, 125.50, 103.35, 52.14, 22.46; EIMS m / z 202. Example 44. Preparation of 4- (1- (4- (trifluoromethoxy) phenyl) -1H-pyrazol-3-yl) benzoic acid (B42)

[00189] Methyl 4- (1H-pyrazol-3-yl) benzoate (2.00 g, 9.89 mmol), 1- bromo-4- (trifluoromethoxy) benzene (2.38 g, 9.88 mmol) , copper (I) iodide (0.28 g, 1.47 mmol), 8-hydroxyquinoline (0.21 g, 1.45 mmol), and cesium carbonate (6.47 g, 19.86 mmol) in DMF / water (11: 1) was heated to 120 ° C for 20 hours. The reaction was cooled, diluted with water and EtOAc, and decanted from the copper solids. The mixture was extracted three times with EtOAc (3 x 150 ml) and the combined organic layers washed with water. The organic layers were dried over anhydrous sodium sulfate, filtered, and absorbed on silica gel. Purification by flash chromatography (0-10% MeOH / dichloromethane) provided 4- (1- (4- (trifluoromethoxy) phenyl) -1H-pyrazol-3-yl) benzoic acid as a brown solid (580 mg, 16 %): 1H NMR (400 MHz, CDCh) δ 8.19 (d, J = 7.7 Hz, 2H), 8.03 (d, J = 7.7 Hz, 2H), 7.98 (d, J = 2.5 Hz, 1H), 7.85 - 7.79 (m, 2H), 7.35 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 2.5 Hz, 1H); 19F NMR (376 MHz, CDCh) δ -58.05; ESIMS m / z 349 ([M + H] +). Example 45. Preparation of 4- (1- (4- (trifluoromethoxy) phenyl) -1H-pyrazol-3-yl) benzoyl azide (B43)

[00190] 4- (1- (4- (trifluoromethoxy) phenyl) -1H-pyrazol-3-yl) benzoic acid (0.58 g, 1.67 mmol) in isopropanol (10.7 mL) was triethylamine (0.30 ml, 2.17 mmol) and diphenylphosphoryl azide (0.47 ml, 2.17 mmol) are added and the reaction was stirred at room temperature for 16 hours. The orange precipitate that formed was filtered through a calcined glass funnel, rinsed with isopropanol, and dried in a vacuum oven to provide 4- (1- (4- (trifluoromethoxy) phenyl) -1H-pyrazole-3- il) benzoyl azide as an orange solid (188 mg, 30%): 1H NMR (400 MHz, DMSO-dθ) δ 8.69 (d, J = 2.6 Hz, 1H), 8.17 - 8.11 (m, 2H), 8.09 - 8.04 (m, 4H), 7.57 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 2.6 Hz, 1H) ; 19F NMR (376 MHz, DMSO-αfe) δ -56.97; ESIMS m / z 374 ([M + H] +). Example 46. Preparation of N - [[(2-isopropylphenyl) amino] thioxomethyl] - / V '- ((4- (1 - (4- (trifluoromethoxy) phenyl) -1 H-pyrazol-3-yl) phenyl) ) urea (Molecule A114)

[00191] A solution of 4- (1- (4- (trifluoromethoxy) phenyl) -1H-pyrazol-3-yl) benzoyl azide (186 mg, 0.50 mmol) in DCE (2.5 mL) was heated to 80 ° C for 2 hours. The reaction was cooled to room temperature and 1- (2-isopropylphenyl) thiourea (97 mg, 0.50 mmol) and cesium carbonate (170 mg, 0.52 mmol) were added. The mixture was stirred at room temperature for 3 days. The reaction was diluted with EtOAc and transferred to a separatory funnel containing water. The aqueous layer was extracted twice with EtOAc. The organic layers were dried over anhydrous sodium sulfate, filtered, and absorbed on silica gel. Purification by flash chromatography (0 to 20% EtOAc / B, where B = 1: 1 dichloromethane / hexanes) provided a yellow solid that contained 10% impurity by LC / MS. Flash reverse phase chromatography (0-100% acetonitrile / water) provided the title compound as a white solid (36.5 mg, 13%): melting point 131 ° C (dec); 1H NMR (400 MHz, CDCh) δ 11.98 (s, 1H), 10.56 (s, 1H), 8.16 (s, 1H), 7.93 (d, J = 2.5 Hz, 1H ), 7.86 (d, J = 8.5 Hz, 2H), 7.83 - 7.76 (m, 2H), 7.47 (d, J = 7.9 Hz, 2H), 7.43 - 7.35 (m, 3H), 7.35 - 7.27 (m, 3H), 6.76 (d, J = 2.5 Hz, 1H), 3.15 (dt, J = 13.7 , 6.8 Hz, 1H), 1.26 (d, J = 6.5 Hz, 6H); 19F NMR (376 MHz, CDCh) δ -58.06; ESIMS m / z 540 ([M + H] +). Example 47. Preparation of ethyl 4- (perfluoroethoxy) benzoate (B44)

[00192] To a 500 ml circular base flask dried in an oven equipped with a stir bar was added 1-bromo-4- (perfluoroethoxy) benzene (9.35 g, 32.1 mmol) and anhydrous THF (200 ml ). The flask was placed under nitrogen and cooled in an ice bath for 10 minutes. A 1.3 M solution of isopropylmagnesium chloride-lithium chloride complex (30 ml, 38.6 mmol) was added over 15 minutes. The ice bath was removed after 1 hour, and the reaction was warmed to room temperature and stirred overnight. GC / MS showed the presence of starting material. The reaction was cooled in an ice bath and 1.3 M isopropyl magnesium chloride-lithium chloride complex (5 mL) was added. The ice bath was removed after 20 minutes and stirred at room temperature for 9 hours. Ethyl chloroformate (3.4 mL, 35.3 mmol) was added in a slow steady stream. The reaction was heated slightly during the addition and was stirred at room temperature overnight. The reaction was diluted with EtOAc and washed with saturated aqueous ammonium chloride. The aqueous layer was extracted three times with EtOAc. The organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated to provide a yellow liquid, which was purified by flash chromatography (0-0, 0-4, 4-10% EtOAc / hexanes) to provide 4- (perfluoroethoxy) ethyl benzoate as a yellow liquid (4.58 g, 50%): 1H NMR (400 MHz, CDCh) δ 8.10 (d, J = 8.8 Hz, 2H), 7.28 (d , J = 8.7 Hz, 2H), 4.39 (q, J = 7.1 Hz, 2H), 1.40 (t, J = 7.1 Hz, 3H); 19F NMR (376 MHz, CDCh) δ -86.05, -87.84; ESIMS m / z 284 ([M + H] +). Example 48. Preparation of 4- (perfluoroethoxy) benzoidrazide (B45)

[00193] To a solution of ethyl 4- (perfluoroethoxy) benzoate (4.58 g, 16.1 mmol) in EtOH (16 ml_) was added hydrazine monohydrate (1.96 ml_, 40.3 mmol) and the reaction was heated to 85 ° C for 36 hours. The reaction was cooled and poured into ice water (100 ml). A white solid gel formed and was filtered through a Büchner funnel under vacuum. The solid was dried in a vacuum oven at 45 ° C overnight to provide 4- (perfluoroethoxy) benzoidrazide as a not entirely white solid (3.177 g, 73%): melting point 117 to 119.5 ° C; 1H NMR (400 MHz, CDCh) δ 7.83 - 7.76 (m, 2H), 7.36 (s, 1H), 7.31 (d, J = 8.8 Hz, 2H), 4.13 (s, 2H); 19F NMR (376 MHz, CDCh) δ -86.01, -87.83; ESIMS m / z 269 [(MH]). Example 49. Preparation of 2- (4- (perfluoroethoxy) phenyl) -1,3,4-oxadiazole (B46)

[00194] A mixture of 4- (perfluoroethoxy) benzoidrazide (3.17 g, 11.7 mmol) in trimethyl orthoformate (11.6 ml_, 106 mmol) and acetic acid (0.13 ml, 2.35 mmol) was heated to 120 ° C for 5 hours. The reaction was diluted with MeOH (15 mL) and poured into a beaker containing ice water (150 mL). The white precipitate was filtered and dried in vacuo in a vacuum oven to provide 166 mg of 2- (4- (perfluoroethoxy) phenyl) -1,3,4-oxadiazole as a not entirely white solid. An orange precipitate formed in the aqueous filtrate and was collected by vacuum filtration and absorbed on silica gel. Purification by flash chromatography (0 - 40% EtOAc / hexanes) gave 2.02 g of 2- (4- (perfluoroethoxy) phenyl) -1,3,4-oxadiazole as a not entirely white solid providing a combined production of 2.186 g (67%): melting point 87 to 89 ° C; 1H NMR (400 MHz, CDCh) δ 8.49 (s, 1H), 8.28 - 8.05 (m, 2H), 7.40 (d, J = 8.9 Hz, 2H); 19F NMR (376 MHz, CDCh) δ -85.98, -87.82; ESIMS m / z 280 ([M + H] +). Example 50. Preparation of methyl 4- (5- (4- (perfluoroethoxy) phenyl) -1,3,4-oxadiazol-2-yl) benzoate (B47)

[00195] A mixture of 2- (4- (perfluoroethoxy) phenyl) -1,3,4-oxadiazole (2,186 g, 7.80 mmol), methyl 4-iodobenzoate (3.07 g, 11.70 mmol) , copper (l) iodide (0.28 g, 1.47 mmol), 1.10-phenanthroline (0.30 g, 1.67 mmol), and cesium carbonate (2.54 g, 7.80 mmol ) in anhydrous DMSO (20 ml) was heated to 100 ° C for 18 hours. The reaction was cooled, diluted with water and extracted three times with EtOAc. The organic layers were dried over anhydrous sodium sulfate, filtered, and absorbed on silica gel. Purification by flash chromatography (0 to 50% EtOAc / hexanes) provided methyl 4- (5- (4- (perfluoroethoxy) phenyl) -1,3,4-oxada diazol-2-yl) benzoate as a white solid (1.08 g, 33%): melting point 185 to 191 ° C; 1H NMR (400 MHz, CDCh) δ 8.25 - 8.19 (m, 6H), 7.41 (t, J = 9.4 Hz, 2H), 3.98 (s, 3H); 19F NMR (376 MHz, CDCh) δ -85.96, -85.98, -87.79; ESIMS m / z 415 ([M + H] +). Example 51. Preparation of 4- (5- (4- (perfluoroethoxy) phenyl) - 1,3,4-oxadiazol-2-yl) benzoic acid (B48)

[00196] To methyl 4- (5- (4- (perfluoroethoxy)) -1,3,4-oxadiazol-2-yl) benzoate (1.07 g, 2.58 mmol) was added MeOH (26 mL ) (the starting material remained partially insoluble). A 2 N NaOH solution (5.2 ml, 10.33 mmol) was added, and the reaction was stirred at room temperature for 18 hours. Stirring was prevented overnight due to the formation of the solid. LC / MS exhibited 25% conversion to the product. The reaction mixture was diluted with MeOH and an additional 2 N NaOH (20 mL) was added and the reaction was heated to 45 ° C for 24 hours. The reaction was cooled and neutralized with 2 N HCI (20 ml). A little MeOH was concentrated in vacuo, causing the product to precipitate. The white precipitate was filtered and dried in vacuo in a vacuum oven at 45 ° C to provide 4- (5- (4- (perfluoroethoxy) phenyl) -1,3,4-oxadiazol-2-yl) benzoic acid as a white solid (760 mg, 90% purity, 66%): melting point 301 at 307 ° C; 1H NMR (400 MHz, DMSO-cfe) δ 13.40 (s, 1H), 8.34 - 8.26 (m, 4H), 8.18 (d, J = 8.6 Hz, 2H), 7 , 68 (d, J = 8.8 Hz, 2H); 19F NMR (376 MHz, DMSO-de) δ -85.25, -86.89; ESIMS m / z 401 ([M + H] +). Example 52. Preparation of 4- (5- (4- (perfluoroethoxy) phenyl) -1,3,4-oxadiazol-2-yl) benzoyl azide (B49)

[00197] To a solution of 4- (5- (4- (perfluoroethoxy) phenyl) -1,3,4-oxadiazol-2-yl) benzoic acid (217 mg, 0.54 mmol) in isopropanol (5.4 ml), triethylamine (0.09 ml, 0.65 mmol) was added and phosphorazidated and diphenyl (0.13 ml, 0.60 mmol) and the reaction was stirred at room temperature for 16 hours. The white precipitate that formed was filtered and dried in a vacuum oven to provide 4- (5- (4- (perfluoroetoxy) phenyl) -1,3,4-oxadiazol-2-yl) benzoyl azide as a white solid (145 mg, 63%): melting point 140 ° C (dec); 1H NMR (400 MHz, DMSO-cfe) δ 8.32 (m, 4H), 8.24 - 8.17 (m, 2H), 7.68 (d, J = 8.9 Hz, 2H); 19F NMR (376 MHz, DMSO-cfe) δ -85.25, -86.89; ESIMS m / z 426 ([M + H] +). Example 53. Preparation of N - [[(2-isopropylphenyl) amino] thioxomethyl] - / V '- ((4- (5- (4- (perfluoroethoxy) phenyl) -1,3,4-oxadiazol-2-yl ) phenyl)) urea (Molecule A96)

[00198] A solution of 4- (5- (4- (perfluoroethoxy) phenyl) -1,3,4-oxadiazol-2-yl) benzoyl azide (278 mg, 0.65 mmol) in DCE (3, 3 ml) was heated to 80 ° C for 3 hours. The reaction was cooled to room temperature and 1- (2-isopropylphenyl) thiourea (131 mg, 0.67 mmol) followed by cesium carbonate (243 mg, 0.75 mmol) was added. The reaction mixture was stirred at room temperature for 18 hours. The reaction was diluted with EtOAc and transferred to a separatory funnel containing aqueous sodium bicarbonate. The aqueous layer was extracted twice with EtOAc. The organic layers were dried over anhydrous sodium sulfate, filtered, and absorbed on silica gel. Purification by flash chromatography (0 to 20% EtOAc / B, where B = 1: 1 dichloromethane / hexanes) gave the title compound as a white powder (43 mg, 11%): melting point 219 ° C ( dec); 1H NMR (400 MHz, DMSO-C / Θ) δ 11.61 (s, 1H), 10.25 (s, 1H), 9.71 (s, 1H), 8.30 - 8.22 (m, 2H), 8.14 (d, J = 8.8 Hz, 2H), 7.71 (d, J = 8.8 Hz, 2H), 7.66 (d, J = 8.7 Hz, 2H) , 7.39 (dd, J = 10.3, 3.9 Hz, 2H), 7.27 (ddd, J = 13.5, 10.6, 6.1 Hz, 2H), 3.07 (heptide , J = 6.8 Hz, 1H), 1.20 (d, J = 6.9 Hz, 6H); 19F NMR (376 MHz, DMSO-cfe) δ -85.25, -86.89; ESIMS m / z 590 ([MH]). Example 54. Preparation of (Z) -1- (3- (2-isopropylphenyl) -4-oxothiazo-lidin-2-ylidene) -3- (4- (5- (4- (perfluoroethoxy) phenyl) -1, 3,4-oxadiazol-2-yl) phenyl) urea (Molecule A102)

[00199] To thiobiuride (135.5 mg, 0.23 mmol) and sodium acetate (80 mg, 0.98 mmol) in ethanol (3 mL) was added methyl 2-bromoacetate (0.05 mL, 0, 49 mmol) and the reaction was heated to 65 ° C for 4 hours. The reaction was diluted with water, and the precipitate was filtered and dried in a vacuum oven. The material was purified by flash chromatography (0 - 20% EtOAc / B, where B = 1: 1 dichloromethane / hexanes) to provide (Z) -1- (3- (2-isopropylphenyl) -4-oxothiazolidin-2- ilidene) -3- (4- (5- (4- (perfluoroethoxy) phenyl) -1,3,4-oxadiazol-2-yl) phenyl) urea as a yellow solid (56 mg, 38%): melting point 244 to 247 ° C; 1H NMR (400 MHz, CDCh) δ 8.21 - 8.15 (m, 2H), 8.06 (d, J = 8.8 Hz, 2H), 7.68 (d, J = 8.8 Hz , 2H), 7.56 - 7.49 (m, 2H), 7.38 (m, 4H), 7.10 (d, J = 7.5 Hz, 1H), 4.01 (d, J = 2.8 Hz, 2H), 2.77 - 2.66 (m, 1H), 1.22 (dd, J = 6.8, 3.1 Hz, 6H); 19F NMR (376 MHz, CDCh) δ -85.96, -87.77; ESIMS m / z 632 ([M + HF).
[00200] The following molecules were made according to the procedures described in example 1, Stage. (E) - ((/ f- (4-methoxyphenyl) carbamimidoyl) thio) methyl (B50) isobutyrate hydrobromide

[00201] mp 129 at 130 ° C; 1H NMR (DMSO-ofe) δ 9.47 (s, NH), 7.23 (s, 2H), 7.07 (d, J = 8.9 Hz, 2H), 6.90 (d, J = 9.0 Hz, 1H), 5.76 (s, 2H), 3.79 (s, 3H), 3.74 (s, 1H), 2.65 (dd, J = 12.0, 5.1 Hz, 1H), 1.13 (d, J = 7.0 Hz, 6H); ESIMS m / z 283 ([M + H] +). (E) - ((AT-mesitylcarbamimidyl) thio) methyl isobutyrate hydrobromide (B51)

[00202] mp 189 to 191 ° C; 1H NMR (DMSO-cfe) δ 11.26 (s, 1H), 9.82 (s, 1H), 8.96 (s, 1H), 7.06 (s, 2H), 5.85 (s, 2H), 2.73 - 2.54 (m, 1H), 2.29 (s, 3H), 2.11 (d, J = 18.4 Hz, 6H), 1.13 (d, J = 7 , 0 Hz, 6H); ESIMS m / z 295 ([M + H] +). (E) - ((N * - (2,6-difluorophenyl) carbamimidoyl) thio) methyl isobutyrate hydrobromide (B52)

[00203] 1H NMR (400 MHz, CDCh) δ 11.25 (s, 1H), 10.46 (s, 1H), 9.17 (s, 1H), 7.45 (s, 1H), 7, 05 (t, J = 8.1 Hz, 2H), 5.78 (s, 2H), 2.76 - 2.64 (m, 1H), 1.29 -1.14 (m, 6H). (E) - ((A / * - (o-tolyl) carbamimidyl) thio) methyl isobutyrate hydrobromide (B53)

[00204] 1H NMR (DMSO-cfe) δ 11.50 (s, 1H), 10.28 (s, 1H), 8.48 (s, 1H), 7.43 - 7.07 (m, 4H) , 5.65 (s, 2H), 2.69 (s, 1H), 2.37 (s, 3H), 1.22 (d, J = 7.0 Hz, 6H); ESIMS m / z 295 ([M + H] +). (E) - ((A /, - (2-ethylphenyl) carbamimidyl) thio) methyl isobutyrate hydrobromide (B54)

[00205] 1H NMR (DMSO-dθ) δ 11.51 (s, 1H), 10.30 (s, 1H), 8.49 (s, 1H), 7.43-7.31 (m, 2H) , 7.27-7.15 (m, 1H), 5.66 (s, 2H), 2.81-2.61 (m, 3H), 1.27-1.21 (m, 9H); ESIMS m / z 295 ([M + H] +). (E) - ((Ar- (2,6-dichlorophenyl) carbamimidoyl) thio) methyl (B55) isobutyrate hydrobromide

[00206] 1H NMR (400 MHz, CDCh) δ 11.48 (s, 1H), 10.55 (s, 1H), 9.05 (s, 1H), 7.47 - 7.41 (m, 2H ), 7.36 (dd, J = 9.2, 6.9 Hz, 1H), 5.75 (s, 2H), 2.69 (m, 1H), 1.25-1.18 (m, 6H); ESIMS m / z 322 ([M + H] +). (E) - ((A /, - (2-ethyl-6-methylphenyl) carbamimidoyl) thio) methyl isobutyrate hydrobromide (B56)

[00207] 1H NMR (400 MHz, CDCh) δ 11.17 (s, 1H), 10.20 (s, 1H), 8.67 (s, 1H), 7.32 - 7.27 (m, 1H ), 7.18 - 7.08 (m, 2H), 5.71 (s, 2H), 2.71 -2.56 (m, 3H), 2.30 (s, 3H), 1.26- 1.18 (m, 9H); ESIMS m / z 295 ([M + H] +). (E) - ((AT- (2- (sec-butyl) phenyl) carbamimidoyl) thio) methyl (B57) isobutyrate hydrobromide

[00208] 1H NMR (400 MHz, CDCh) 7.46 - 7.39 (m, 1H), 7.37 - 7.32 (m, 1H), 7.23 (t, J = 7.1 Hz, 1H), 7.17 (d, J = 7.6 Hz, 1H), 5.64 (s, 2H), 2.92 (dd, J = 13.9, 7.0 Hz, 1H), 2, 68 (dt, J = 14.0, 7.0 Hz, 1H), 1.70 - 1.60 (m, 2H), 1.23 (t, J = 6.7 Hz, 9H), 0.84 (t, J = 7.4 Hz, 3H); ESIMS m / z 332 ([M + Na] +). Example 55. Preparation of 1- (4- (perfluoropropyl) phenyl) -3- (p-tolyl) - 1 H-1,2,4-triazole (B58)

[00209] Heptafluoropropyl-1-iodopropane (3.14 g, 10.6 mmol), 1-iodo-4-bromobenzene (2.0 g, 7.07 mmol), and copper (powder: 1.123 g, 17.7 mmol) were combined in 16 ml of DMSO in a 20 ml microwave tube, and the solution was stirred and heated to 175 ° C for 90 min. The cooled solution was then extracted with 2 X 30 ml of hexanes, and the combined organic layer was washed with water, dried and concentrated to provide 2.0 grams of a yellow oil. This raw material, which consisted of a mixture of 4-heptafluoropropyl-iodobenzene and 4-heptafluoropropyl-bromobenzene, was combined with 3- (p-tolyl) -1H-1,2,4-triazole (1.0 g, 6 , 28 mmol), cesium carbonate (6.14 g, 18.9 mmol), Cul (0.12 g, 0.63 mmol), and quinolin-8-ol (0.091 g, 0.63 mmol) in 16 ml of 90:10 DMF-water, and the solution was heated to 125 ° C for 8 hours. The cooled solution was then poured into 60 ml of 2N aqueous NhLOH solution, and the resulting precipitate was filtered and air dried. This material was heated in 50 ml of MeOH, filtered, and the filtrate diluted with 30 ml of water. The resulting solid was filtered and air dried to provide 1- (4- (perfluoropropyl) phenyl) -3- (p-tolyl) -1 H-1,2,4-triazole as a white solid (1.03 g, 39%): melting point 140 to 143 ° C; 1H NMR (400 MHz, CDCh) δ 8.66 (s, 1H), 8.10 (d, J = 8.1 Hz, 2H), 7.94 (d, J = 8.9 Hz, 2H), 7.76 (d, J = 8.5 Hz, 2H), 7.30 (dt, J = 8.0, 0.7 Hz, 2H), 2.43 (s, 3H); ESIMS m / z 405 ([M + H] +). Example 56. Preparation of 4- (1- (4- (perfluoropropyl) phenyl) - 1 H-1,2,4-triazol-3-yl) benzoic acid (B59)

[00210] A solution of tolyl triazole (1.0 g, 2.48 mmol) in 6 mL of AcOH was heated to 60 ° C, and cyclic ammonium nitrate (4.50 g, 8.21 mmol) in 3 mL of water was added over 10 minutes. Heating was continued for 1 hour, then the solution was cooled and diluted with 30 ml of water. The liquid was decanted from a light yellow viscous solid which formed over 30 min. This residue was then combined with 10 ml of dioxane and 3 ml of 50% aqueous KOH, and heated at 75 to 80 ° C for 2 hours. The solution was cooled and diluted with 20 ml of water. The resulting solid was filtered and then re-dissolved in 15 ml of acetonitrile, and sodium bromate (1.12 g, 7.44 mmol) and sodium bisulfide (0.298 g, 2.48 mmol) were added. The solution was heated to reflux for 2 hours, then cooled and diluted with 10 ml of water. A white precipitate formed, which was filtered and air dried to provide 4- (1- (4- (perfluoropropyl) phenyl) -1H-1,2,4-triazol-3-yl) benzoic acid as a white powder (472 mg, 41%): melting point 225 ° C; 1H NMR (400 MHz, DMSO-dβ) δ 9.60 (s, 1H), 8.29 - 8.20 (m, 4H), 8.13 - 8.06 (m, 2H), 7.96 ( d, J = 8.7 Hz, 2H); ESIMS m / z 434 ([M + H] +). Example 57. Preparation of 4- (1- (4- (perfluoropropyl) phenyl) -1H-1,2,4-triazol-3-yl) benzoyl azide (B60)

[00211] 4- (1- (4- (Perfluoropropyl) phenyl) -1H-1,2,4-triazol-3-yl) benzoic acid (400 mg, 0.92 mmol) was dissolved in 7 ml of isopropanol and treated with diphenylphosphoryl azide (0.300 g, 1.09 mmol) and triethylamine (0.200 g, 2.0 mmol). The solution was allowed to stir for 6 hours, then it was cooled to 0 ° C and the resulting solid was filtered, washed with a minimum amount of 'PrOH, and dried under high vacuum to provide the azide as a not entirely white solid ( 0.120 g, 30%). This solid was also not characterized, but used directly in the subsequent Curtius recombination to prepare the A113 molecule, using the conditions described in Example 39. Example 58. Preparation of (Z) -1- (3-mesityl-4-methylthiazole -2 (3H) - ilidene) -3- (4- (1 - (4- (trifluoromethoxy) phenyl) -1 H-1,2,4-triazol-3-yl) phenyl) urea (Molecule A43)

[00212] To the free thiobiuride (100 mg, 0.185 mmol) in 3 ml_ of butanone was added triethylamine (0.052 ml_, 0.370 mmol) followed by chloroacetone (0.021 ml_, 0.259 mmol). The solution was heated to reflux for 20 hours, then it was cooled, diluted with 20 ml_ CH2 Cl2, washed with water (10 ml_), dried and concentrated in vacuo. Chromatography (silica, 0-100% EtOAc-hexanes) gave the desired product as a yellow viscous oil (0.92 g, 84%): 1H NMR (400 MHz, CDCh) δ 8.55 (s, 1H) , 8.17 (d, J = 8.7 Hz, 2H), 7.85 - 7.68 (m, 5H), 7.37 (d, J = 8.3 Hz, 2H), 7.02 ( s, 2H), 6.35 (d, J = 0.9 Hz, 1H), 2.43 (s, 3H), 2.34 (s, 3H), 2.17 (s, 6H); 19F NMR (376 MHz, CDCh) □ -58.01 (s); ESIMS m / z 579 ([M + H] +).
[00213] The A42 molecule in Table 1 was made according to the procedures described in Example 58. Example 59. Preparation of 3-bromo-1- (4- (trifluoromethoxy) phenyl) - 1H-1,2,4-triazole (B61)

[00214] To a 250 ml reaction flask was added 3-bromo-1H-1,2,4-triazole (5 g, 33.8 mmol), copper (l) iodide (0.644 g, 3.38 mmol) ) and cesium carbonate (11.01 g, 33.8 mmol). The flask was evacuated / refilled with N2, then DMSO (33.8 ml) and 1-iodo-4- (trifluoromethoxy) benzene (4.87 g, 16.90 mmol) were added. The reaction mixture was heated at 100 ° C for 20 hours. The reaction was cooled to room temperature, diluted with EtOAc and filtered through a plug of Celite. Celite was also washed with EtOAc. Water was added to the combined organics, and the layers were separated. The aqueous phase was neutralized to pH 7, and also extracted with EtOAc. The combined organics were concentrated in vacuo. Purification by flash chromatography (silica / EtOAc / Hex) produced 3-bromo-1- (4- (trifluoromethoxy) phenyl) -1H- 1,2,4-triazole as a not entirely white solid (3.78 g , 12.27 mmol, 72.6%): melting point 69 at 70 ° C; 1H NMR (400 MHz, CDCh) δ 8.44 (s, 1H), 7.70 (d, J = 8.9 Hz, 2H), 7.38 (d, J = 8.5 Hz, 2H); 19F NMR (376 MHz, CDCh) δ -58.04; EIMS m / z 307. Example 60. Preparation of methyl 2-methyl-4- (1- (4- (trifluoromethoxy) phenyl) - 1H-1,2,4-triazol-3-yl) benzoate (B62)

[00215] Ao 3-bromo-1- (4- (trifluoromethoxy) phenyl) -1H-1,2,4-triazole (0.496 g, 1.609 mmol), 2-methyl-4- (4,4,5,5 methyl tetramethyl-1,3,2-dioxaborolan-2-yl) benzoate (0.466 g, 1.689 mmol), sodium bicarbonate (0.405 g, 4.83 mmol) and tetracis (triphenylphosphine) palladium (0.186 g, 0.171 mmol) ) in a 2.0 ml microwave vial, dioxane (6 ml) and water (1.5 ml) were added. The reaction was covered and placed in a microwave reactor Biotage® for 30 minutes at 140 ° C. The reaction mixture was then diluted with EtOAc and washed with water. The aqueous layer was extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered and concentrated. Purification by flash column chromatography gave the title compound as a white solid (0.376 g, 0.997 mmol, 62%): 1H NMR (400 MHz, CDCh) δ 8.59 (s, 1H), 8.10 (dt, J = 1.6, 0.7 Hz, 1H), 8.09 - 8.00 (m, 2H), 7.84 - 7.78 (m, 2H), 7.44 - 7.37 (m, 2H), 3.93 (s, 3H), 2.70 (s, 3H); 19F NMR (376 MHz, CDCh) δ -58.02; ESIMS m / z 378 ([M + H] +). Example 61. Preparation of 2-methyl-4- (1- (4- (trifluoromethoxy) phenyl) -1 H-1,2,4-triazol-3-yl) benzoic acid (B63)

[00216] The two batches of methyl 2-methyl-4- (1- (4- (trifluoromethoxy) phenyl) - 1 / - / - 1,2,4-triazol-3-yl) benzoate (0.452 g, 1.188 mmol) in a 250 ml circular base flask equipped with a stir bar was added MeOH (12 ml), THF (12 ml) and 2N sodium hydroxide (5.99 ml, 11.98 mmol). The reaction was stirred overnight. The reaction mixture was diluted with water and acidified with 1N HCI. The solid was extracted with EtOAc (3x). The organic layer was dried over MgSO4, filtered and concentrated providing the title compound as a yellow solid (0.412 g, 1.134 mmol, 95%): 1H NMR (300 MHz, DMSO-dβ) δ 12.94 (s, 1H), 9.43 (s, 1H), 8.14 - 8.03 (m, 2H), 8.03 - 7.89 (m, 3H), 7.61 (d, J = 8.7 Hz, 2H) , 2.60 (s, 3H); 19F NMR (376 MHz, DMSO-dβ) δ -56.95; ESIMS m / z 364 ([M + H] +). Example 62. Preparation of 2-methyl-4- (1- (4- (trifluoromethoxy) phenyl) - 1H-1,2,4-triazol-3-yl) benzoyl azide (B64)

[00217] To 2-methyl-4- (1- (4- (trifluoromethoxy) phenyl) -1H-1,2,4-triazol-3-yl) benzoic acid (0.412 g, 1.134 mmol) in a vial 100 ml circular base equipped with a stir bar under N2, isopropyl alcohol (11 ml), triethylamine (0.205 ml, 1.474 mmol) and diphenyl phosphorazidate (0.319 ml, 1.474 mmol) were added. The reaction was stirred at room temperature overnight. The resulting solid was filtered, washed with isopropyl alcohol followed by hexanes and dried in vacuo providing the title compound as a white solid (0.294 g, 0.757 mmol, 67%): 1H NMR (300 MHz, CDCh) δ 8.60 ( s, 1H), 8.13 (s, 1H), 8.11 - 8.02 (m, 2H), 7.84 - 7.77 (m, 2H), 7.40 (d, J = 8, 6 Hz, 2H), 2.74 (s, 3H); 19F NMR (376 MHz, CDCh) δ -58.02; ESIMS m / z 389 ([M + HF). Example 63. Preparation of M - [[(2-isopropylphenyl) amino] thioxomethyl] - N '- (2-methyl (4- (1 - (4- (trifluoromethoxy) phenyl) -1 H-1,2,4- triazol-3-yl) phenyl)) urea (Molecule A122)

[00218] A 2-methyl-4- (1- (4- (trifluoromethoxy) phenyl) -1H-1,2,4-triazol-3-yl) benzoyl azide (0.294 g, 0.757 mmol) in a 25 vial ml-equipped with a stir bar and a Vigreux column, 1,2-dichloroethane (4 ml) was added. The reaction was heated to 80 ° C. After the formation of isocyanate, the reaction was cooled to room temperature. To the reaction was added 1- (2-isopropylphenyl) thiourea (0.162 g, 0.833 mmol) and cesium carbonate (0.271 g, 0.833 mmol). The reaction was stirred overnight. The reaction mixture was diluted with EtOAc and washed with saturated sodium bicarbonate. The aqueous layer was extracted with EtOAc. The combined organic layers were dried over MgSOzi, filtered and concentrated. Purification by flash column chromatography gave the title compound as a white solid (0.243 g, 0.438 mmol, 58%): 1H NMR (400 MHz, DMSO-dβ) δ 11.74 (s, 1H), 10.71 ( s, 1H), 9.39 (s, 1H), 8.83 (s, 1H), 8.13 - 8.04 (m, 2H), 8.04 - 7.88 (m, 3H), 7 , 68 - 7.56 (m, 2H), 7.47 - 7.35 (m, 2H), 7.35 - 7.27 (m, 1H), 7.27 - 7.21 (m, 1H) , 3.06 (hept, J = 6.8 Hz, 1H), 2.37 (s, 3H), 1.19 (d, J = 6.8 Hz, 6H); 19F NMR (376 MHz, DMSO-dβ) δ -56.97; ESIMS m / z 555 ([M + H] +). Example 64. Preparation of (Z) -1- (3- (2-isopropylphenyl) -4-oxothiazolidin-2-ylidene) -3- (2-methyl-4- (1 - (4- (trifluoromethoxy) phenyl ) -1 H-1,2,4-triazol-3-yl) phenyl) urea (Molecule A123)

[00219] AA / - [[(2-isopropylphenyl) amino] thioxomethyl] -A / '- (2-methyl (4- (1- (4- (trifluoromethoxy) phenyl) -1H-1,2,4-triazole -3-yl) phenyl)) urea (0.193 g, 0.348 mmol) in a 25 ml flask equipped with a stir bar and Vigreux column, sodium acetate (0.114 g, 1.392 mmol), EtOH (4 mL) and 2 -methyl bromoacetate (0.066 ml, 0.696 mmol). The reaction was stirred at 60 ° C overnight. The reaction was cooled and the solid was filtered, washed with EtOH, followed by diethyl ether in vacuo providing the title compound as a white solid (0.124 g, 0.209 mmol, 60%): 1H NMR (400 MHz, CDCh) δ 8, 53 (s, 1H), 8.18 (d, J = 8.6 Hz, 1H), 8.06 - 8.01 (m, 1H), 7.98 (s, 1H), 7.82 - 7 , 76 (m, 2H), 7.53 - 7.48 (m, 2H), 7.41 - 7.34 (m, 3H), 7.13 - 7.06 (m, 2H), 3.99 (s, 2H), 2.73 (hept, J = 6.8 Hz, 1H), 2.25 (s, 3H), 1.27 - 1.22 (m, 6H); 19F NMR (376 MHz, CDCh) δ -58.03; ESIMS m / z 595 ([M + H] +). Example 65. Preparation of W - ((1H-benzo [d] [1,2,3] triazol-1-yl) methyl) -4- (1 - (4- (trifluoromethoxy) phenyl) -1 H- 1,2,4-triazol-3-yl) aniline (B65)

[00220] To a 100 ml vial was added benzotriazole (2.083 g, 17.5 mmol) and 4- (1- (4- (trifluoromethyl) phenyl) -1H-1,2,4-triazol-3-yl) aniline (5.6 g, 17.5 mmol), and the solids were melted with a heat gun. EtOH (26 ml) was quickly added and the mixture was stirred at the same time as formaldehyde (1.3 ml of a 37% aqueous solution, 47.2 mmol) was added via syringe. The solution was allowed to stir at room temperature for 30 minutes, then it was heated to 40 ° C for another 30 minutes, then allowed to cool to room temperature before collecting the solid product by vacuum filtration. After washing the solid with EtOH and hexanes, A / - ((1 H-benzo [d] [1,2,3] triazol-1-i) methyl I) -4- (1 - (4- ( trifluoromethoxy- (phenyl) -1H-1,2,4-triazol-3-yl) crude aniline, which was used directly without further purification (3.79 g, 49%): 1H NMR (400 MHz, CDCh) δ 8.49 (s, 1H), 8.06 (d, J = 8.4 Hz, 1H), 8.02 (d, J = 8.7 Hz, 2H), 7.76 (d, J = 9.0 Hz, 2H), 7.64 (d, J = 8.3 Hz, 1H), 7.48 (ddd, J = 8.3, 7.0, 1.0 Hz, 1H), 7, 40 - 7.33 (m, 2H), 6.96 (d, J = 8.8 Hz, 2H), 6.15 (d, J = 7.2 Hz, 2H), 5.07 (t, J = 7.1 Hz, 1H). Example 66. Preparation of N-methyl-4- (1- (4- (trifluoromethyl) phenyl) -1H- 1,2,4-triazol-3-yl) aniline (B66)

[00221] To a solution of / V - ((1H-benzo [d] [1,2,3] triazol-1-yl) methyl) -4- (1- (4- (trifluoromethoxy) phenyl) -1H- 1,2,4-triazol-3-yl) aniline (3.78 g, 8.37 mmol) in THF (25 mL) sodium borohydride (0.475 g, 12.56 mmol) was added slowly with stirring under N2 . The solution was allowed to stir at room temperature for 1 hour, then it was heated to reflux for 3.5 hours. After cooling to room temperature, the solution was poured into water (25 ml) and extracted with 50 ml of ether (2x). Drying and concentration of the organic layer gave A / -methyl-4- (1 - (4- (trifluoromethyl) phenyl) -1 H-1,2,4-triazol-3-yl) aniline as an orange solid (2 , 49 g, 86%): melting point 106 to 113 ° C; ESIMS m / z 335 ([M + H] +). Example 67. Preparation of / V- (methyl (4- (1- (4- (trifluoromethoxy) phenyl) - 1H-1,2,4-triazol-3-yl) phenyl) carbamothioyl) benzamide (B67)

[00222] To a solution of W-methyl-4- (1- (4- (trifluoromethyl) phenyl) -1H- 1,2,4-triazol-3-yl) aniline (2.0 g, 5.98 mmol ) in acetone, benzoyl isothiocyanate (0.847 g, 6.28 mmol) was added via syringe, and the solution was heated to 50 ° C for 8 hours, then the solution was cooled and concentrated in vacuo to provide A / - (methyl (4- (1- (4- (trifluoromethoxy) phenyl) -1H-1,2,4-triazol-3-yl) phenyl) carbamothioyl) benzamide as a yellow solid (2.9 g, 96 %): melting point 166 to 169 ° C; 1H NMR (400 MHz, CDCh) δ 8.53 (s, 1H), 8.36 (s, 1H), 8.20 (d, J = 8.6 Hz, 2H), 7.76 (d, J = 9.0 Hz, 2H), 7.60 (d, J = 7.5 Hz, 1H), 7.52 - 7.42 (m, 4H), 7.38 (dt, J = 8.0, 1.0 Hz, 2H), 3.82 (s, 3H); ESIMS m / z 497 ([M + HF). Example 68. Preparation of 1-methyl-1- (4- (1- (4- (trifluoromethoxy) phenyl) -1 H-1,2,4-triazol-3-yl) phenyl) thiourea (B68)

[00223] To a 100 ml_ circular flask containing MeOH (23 ml_) was added A / - (methyl (4- (1- (4- (trifluoromethoxy) phenyl) -1H-1,2,4-triazole- 3-yl) phenyl) carbamothioyl) benzamide (2.8 g, 5.63 mmol) and sodium hydroxide (5.6 ml of a 2 N solution, 11.3 mmol), and the solution was heated to 65 ° C for 3.5 hours. Another 20 ml (40 mmol) of 2N NaOH was then added and heating was continued for 6 hours. Upon cooling the solution was neutralized by the addition of 2N HCI, and the resulting yellow solid was collected by vacuum filtration to provide 1-methyl-1- (4- (1- (4- (trifluoromethoxy) phenyl) -1H-1 , 2,4-triazol-3-yl) phenyl) thiourea as a yellow solid (1.073 g, 47%): melting point 142 to 152 ° C; 1H NMR (400 MHz, CDCh) δ 8.59 (s, 1H), 8.36 - 8.24 (m, 2H), 7.81 (d, J = 9.0 Hz, 2H), 7.46 - 7.33 (m, 4H), 5.62 (s, 2H), 3.73 (s, 3H); ESIMS m / z 393 ([M + H] +). Example 69. Preparation of 2- (methyl (4- (1- (4- (trifluoromethoxy) phenyl) - 1 H-1,2,4-triazol-3-yl) phenyl) amino) thiazol-4,5-dione (B69)

[00224] To a flask containing EtOAc (30 ml_) was added 1-methyl- 1- (4- (1- (4- (trifluoromethoxy) phenyl) -1 H-1,2,4-triazol-3-yl) phenyl) thiourea (0.600 g, 1.52 mmol) and triethylamine (510 pl, 3.66 mmol). A solution of oxalyl chloride (467 ml, 5.34 mmol) in EtOAc (24 ml) was added and the solution was stirred at room temperature for 15 minutes. Evaporation of the solvent in vacuo left a yellowish white solid which was dissolved in 50 ml of dichloromethane and washed with water (3 X 25 ml). The organic layer was dried (MgSÜ4) and concentrated to provide 2- (methyl (4- (1 - (4- (trifluoromethoxy) phenyl) -1 H-1,2,4-triazol-3-i I) ) amino) thiazol-4,5-dione as an orange solid (632 mg, 92%): melting point 114 to 118 ° C; 1H NMR (400 MHz, CDCh) δ 8.62 (s, 1H), 8.36 (d, J = 8.7 Hz, 2H), 7.82 (d, J = 9.1 Hz, 2H), 7.50 - 7.34 (m, 4H), 3.82 (s, 3H); ESIMS m / z 448 ([M + H] +). Example 70. Preparation of W - [[(2-isopropylphenyl) amino] thioxomethyl] - N -methyl-Af- (4- (1 - (4- (trifluoromethoxy) phenyl) -1 H-1,2,4-trlazole -3- yl) phenyl)) urea (A124)

[00225] A solution of 2- (methyl (4- (1- (4- (trifluoromethoxy) phenyl) -1H- 1,2,4-triazol-3-yl) phenyl) amino) thiazol-4,5-dione (615 mg, 1.38 mmol) in toluene (16 mL) was heated to 100 ° C for 25 minutes, then cooled to 0 ° C and 2-isopropylaniline (0.212 mL, 1.51 mmol) in acetone (4 mL ) was added under N2. After 2 hours, the solution was allowed to warm to room temperature and then concentrated. Purification by flash column chromatography (EtOAc-hexanes) provided N- [[(2-isopropylphenyl) amino] thioxomethyl] -A / '- methyl- / V' - (4- (1- (4- (trifluorometho - xi) phenyl) -1H-1,2,4-triazol-3-yl) phenyl)) urea as a light orange oil (300 mg, 40%); 1H NMR (400 MHz, CDCh) δ 12.03 (s, 1H), 8.60 (s, 1H), 8.36 (d, J = 8.7 Hz, 1H), 7.89 (s, 1H ), 7.81 (d, J = 9.1 Hz, 1H), 7.52 - 7.48 (m, 1H), 7.46 (d, J = 8.7 Hz, 1H), 7.41 (dt, J = 7.9, 1.0 Hz, 2H), 7.36 (dd, J = 7.8, 1.7 Hz, 1H), 7.30 (td, J = 7.5, 1 , 5 Hz, 1H), 7.25 - 7.20 (m, 1H), 3.40 (s, 3H), 1.27 (d, J = 6.9 Hz, 6H); ESIMS m / z 555 ([M + HD- Example 71. Preparation of (Z) -3- (3- (2-isopropylphenyl) -4-oxothiazolin-din-2-ylidene) -1-methyl-1 - <4 - (1 - (4- (trifluoromethoxy) phenyl) -1 H-1,2,4-triazol-3-yl) phenyl) urea (A125)

[00226] The conditions described in Example 14 were used to convert A / - [[(2-isopropylphenyl) amino] thioxomethyl] -A / '- methyl-A /' - (4- (1 - (4- (trifluoromethoxy) phenyl) -1H-1,2,4-triazol-3-yl) phenyl)) urea in (Z) -3- (3- (2-isopropylphenyl) -4-oxothiazolidin-2-ylidene) -1-methyl- 1 - (4- (1 - (4- (trifluoromethoxy) phenyl) -1 / 7-1,2,4-triazol-3-yl) phenyl) urea, which was isolated as a yellow oil (19 mg , 34%): δ 1H NMR (400 MHz, CDCh) δ 8.58 (s, 1H), 8.17 (s, 1H), 7.83 (d, J = 8.9 Hz, 2H), 7 , 73 (d, J = 8.1 Hz, 2H), 7.42 (d, J = 8.8 Hz, 3H), 7.22 (d, J = 7.6 Hz, 1H), 7.17 -7.07 (m, 1H), 6.85 (dd, J = 28.9, 8.0 Hz, 2H), 3.95 (d, J = 2.5 Hz, 3H), 3.37 ( s, 2H), 2.50 (d, J = 7.1 Hz, 1H), 1.05 (d, J = 6.9 Hz, 3H), 0.79 (d, J = 6.8 Hz, 3H); ESIMS m / z 595 ([M + H] +). Table 1: Structures for compounds













Table 2: Analytical data for the compounds in Table 1.


























All of the 1H NMR data evaluated in 400 MHz CDCh unless otherwise noted Example A: Bioassays on beet caterpillar (“BAW”) and corn worm (“CEW”)
[00227] BAW has few effective parasites, diseases, or predators to decrease its population. BAW infests many weeds, trees, grasses, vegetables, and field crops. In several places, it is of economic interest in asparagus, cotton, corn, soybeans, tobacco, alfalfa, sugar beets, peppers, tomatoes, potatoes, onions, peas, sunflowers, and citruses, among other plants. CEW is known to attack corn and tomatoes, but it also attacks artichoke, asparagus, cabbage, cantaloupe, collards, string beans, cucumbers, eggplant, lettuce, lima beans, melon, okra, peas, peppers, potatoes, pumpkin, snap beans, spinach, pumpkin, sweet potatoes, and watermelons, among other plants. CEW is also known to be resistant to certain insecticides. Consequently, because of the factors above, control of these pests is important. In addition, the molecules that control these pests (BAW and CEW), which are known as chewing pests, are useful in controlling other pests that chew plants.
[00228] Certain molecules described in this document have been tested against BAW and CEW using the procedures described in the following examples. In the results report, the “BAW & CEW evaluation table” was used (See Table section). BAW Bioassays (Spodoptera exígua)
[00229] The BAW bioassays were conducted using a 128-well diet tray assay. One to five second instar BAW larvae were placed in each well (3 mL) of the diet tray that was previously loaded with 1 mL of artificial diet which contained 50 pg / cm2 of the test compound (dissolved in 50 pL of 90: 10 of acetone-water mixture) was applied (to each of the eight wells) and then allowed to dry. The trays were covered with a clear self-adhesive cover and kept at 25 ° C, 14:10 chiaroscuro for five to seven days. The mortality percentage was recorded for the larvae in each cavity; activity in the eight wells was then measured. The results are shown in the table entitled “Table ABC: Biological Results” (see Tables Section). Bioassays in CEW (Helicoverpa zea)
[00230] The CEW bioassays were conducted using a 128-well diet tray assay. One to five second instar CEW larvae were placed in each well (3 ml_) of the diet tray that was previously loaded with 1 ml_ of artificial diet which contained 50 pg / cm2 of the test compound (dissolved in 50 pL of 90: 10 of acetone-water mixture) was applied (to each of the eight wells) and then allowed to dry. The trays were covered with a clear self-adhesive cover and kept at 25 ° C, 14:10 light-dark for five to seven days. The mortality percentage was recorded for the larvae in each cavity; activity in the eight wells was then measured. The results are shown in the table entitled “Table ABC: Biological Results” (See Table Section). Example B: Bioassays on Green Peach Aphid (“GPA”) (Myzus persicae).
[00231] GPA is the most significant aphid pest of peach trees, causing slow growth, withering leaves, and the death of various tissues. It is also dangerous because it acts as a vector for the transport of plant viruses, such as potato Y virus and potato leaf winder virus to members of the Solanaceae herb / potato family, and various mosaic viruses to many other crops. foods. GPA attacks such plants as broccoli, burdock, cabbage, carrots, cauliflower, daikon, eggplant, green beans, lettuce, macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, and zucchini, among other plants. GPA also attacks many ornamental crops such as carnation, chrysanthemum, blooming white cabbage, poinset-aunt, and roses. GPA has developed resistance to many pesticides. Consequently, because of the above factors, controlling this plague is important. In addition, the molecules that control this plague (GPA), which is known as a suction plague, are useful in controlling other pests that suck on plants.
[00232] Certain molecules described in this document have been tested against GPA using the procedures described in the following example. In the results report, the “GPA Evaluation Table” was used (See Tables Section).
[00233] The cabbage seedlings developed in 3-inch pots, with 2-3 small (3-5 cm) true leaves, were used as the test substrate. The seedlings were infested with 20-50 GPA (nymph and wingless adduct stages) one day before chemical application. Four pots with individual seedlings were used for each treatment. The test compounds (2 mg) were dissolved in 2 ml of acetone / MeOH solvent (1: 1), forming raw material solutions of 1000 ppm of test compound. The raw material solutions were diluted 5X with 0.025% Tween 20 in H2O to obtain the solution in 200 ppm of test compound. A manual vacuum cleaner was used to spray a solution on both sides of the cabbage leaves until it drained. The reference plants (check the solvent) were sprayed with the diluent containing only 20% by volume of acetone / MeOH solvent (1: 1). The treated plants were kept in a containment room for three days at approximately 25 ° C and relative ambient humidity (RH) before classification. The evaluation was carried out containing the number of live aphids per plant under a microscope. The percentage of control was measured using Abbott's correction formula (W.S. Abbott, “A Method of Computing the Effectiveness of an Insecticide” J. Econ. Entomol. 18 (1925), pp, 265-267) as follows. % Control corrected = 100 * (X - Y) / X where X = number of live aphids on solvent checking plants and Y = No. of live aphids on treated plants
[00234] The results are indicated in the table entitled “Table ABC: Biological Results” (See Tables Section). Example C: Bioassays on the yellow fever mosquito “YFM” (Aedes aegypti).
[00235] YFM prefers to feed on humans during the day and is most often found in or near human dwellings. YFM is a vector for transmitting various diseases. It is a mosquito that can spread dengue fever and yellow fever virus. Yellow fever is the second most dangerous mosquito-borne disease after malaria. Yellow fever is an acute viral hemorrhagic disease and up to 50% of severely affected people without treatment will die of yellow fever. There are an estimated 200,000 cases of yellow fever causing 30,000 deaths worldwide each year. Dengue fever is a serious viral disease; it is sometimes called "breakbone fever" or "break-heart fever" because of the severe pain it can produce. Dengue fever kills about 20,000 people annually. Consequently, because of the above factors, control of this plague is important. In addition, the molecules that control this plague (YFM), which are known as a suction plague, are useful in controlling other pests that cause human and animal suffering.
[00236] Certain molecules described in this document have been tested against YFM using the procedures described in the following paragraph. In the results report, the “YFM Evaluation Table” was used (See the Table Section).
[00237] Master plates containing 400 pg of a molecule dissolved in 100 pL of dimethyl sulfoxide (DMSO) (equivalent to a 4000 ppm solution) are used. A master plate of grouped molecules contains 15 pL per well. To this plate, 135 pL of a 90:10 water: acetone mixture is added to each well. A robot (Biomek® NXP Laboratory Automation Workstation) is programmed to dispense 15 pL of aspirations from the master plate into an empty 96-well shallow plate (daughter plate). There are 6 reps, (daughter plates) created by the master. The daughter plates created are then immediately infested with YFM larvae.
[00238] On the previous day the plates must be treated, mosquito eggs are placed in Millipore water containing liver powder to start the incubation (4 g. In 400 mL). After the daughter plates are created using the robot, they are infested with 220 pL of the liver powder / larval mosquito mixture (about 1 day old larvae). After the plates are infested with mosquito larvae, a non-evaporative buffer is used to cover the plate to reduce drying. The plates are kept at room temperature for 3 days before sorting. After 3 days, each cavity is observed and classified based on mortality.
[00239] The results are indicated in the table entitled “Table ABC: Biological Results” (See Tables Section). PESTICIDALLY ACCEPTABLE ACID ADDITION SALES, DE-RIVATED FROM SALT, SOLVATES, ESTER DERIVATIVES, POLYMORPHOS, ISOTOPES AND RADIONUCLIDES
[00240] Formula One molecules can be formulated into pesticide-acceptable acid addition salts. As a non-limiting example, an amine function can form salts with hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic, succinic, tartaric, lactic, gluconic acids, ascorbic, maleic, aspartic, benzenesulfonic, methanesulfonic, ethanesulfonic, hydroxymethanesulfonic, and hydroxyethanesulfonic. In addition, as a non-limiting example, an acid function can form salts including those derived from alkaline earth metals or alkali and those derived from ammonia and amines. Examples of preferred cations include sodium, potassium, and magnesium.
[00241] Formula One molecules can be formulated into salt derivatives. As a non-limiting example, a salt derivative can be prepared by contacting a free base with a sufficient amount of the desired acid to produce a salt. A free base can be regenerated by treating the salt with a suitable dilute aqueous base solution such as dilute aqueous sodium hydroxide (NaOH), potassium carbonate, ammonia, and sodium bicarbonate. As an example, in many cases, a pesticide, such as 2,4-D, is made more soluble in water by converting it to its dimethylamine salt.
[00242] Formula One molecules can be formulated into stable complexes with a solvent, such that the complex remains intact after the uncomplexed solvent is removed. These complexes are often referred to as "solvates." However, it is particularly desirable to form stable hydrates with water as the solvent.
[00243] Formula One molecules can be made into ester derivatives. These ester derivatives can then be applied in the same way as the molecules described in this document are applied.
[00244] Formula One molecules can be made as several polymorphic crystals. Polymorphism is important in the development of agrochemicals since different crystal polymorphs or structures of the same molecule can have vastly different physical properties and biological performances.
[00245] Formula One molecules can be made with different isotopes. Of particular importance are molecules having 2H (also known as deuterium) in place of 1H.
[00246] Formula One molecules can be made with different radionuclides. Of particular importance are molecules having 14C. STEREQISOMERQS
[00247] Formula One molecules can exist as one or more stereoisomers. In this way, certain molecules can be produced as racemic mixtures. It will be appreciated by those skilled in the art that a stereoisomer can be more active than other stereoisomers. Individual stereoisomers can be obtained by known selective synthetic procedures, by conventional synthetic procedures using resolved starting materials, or by conventional resolution procedures. Certain molecules described in this document can exist as two or more isomers. The various isomers include geometric isomers, diastereomers, and enantiomers. Thus, the molecules described in this document include geometric isomers, racemic mixtures, individual stereoisomers, and optically active mixtures. It will be appreciated by those skilled in the art that an isomer may be more active than others. The structures described in the present description are represented in only one geometric shape for clarity, however they are intended to represent all the geometric shapes of the molecule. COMBINATIONS
[00248] Formula One molecules can also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more compounds having acaricide, algaecide, avicide, bactericide, fungicide, herbicide, insecticide, molluscicide, nematicide, rodenticide, or virucide. In addition, Formula One molecules can also be used in combination (such as, in a conventional mixture, or a simultaneous or sequential application) with compounds that are antiallitric, bird repellants, chemosterilizers, herbicide protectors, insect attractants , insect repellents, mammal repellents, mating disrupters, plant activators, plant growth regulators or synergists. Examples of such compounds in the above groups that can be used with the Formula One molecules are - (3-ethoxypropyl) mercury bromide, 1,2-dichloropropane, 1,3-dichloropropene, 1-methylcyclopropene, 1-naphthol, 2- (octylthium) ethanol, 2,3,5-triiodiodobenzoic acid, 2,3,6-TBA, 2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6- TBA-potassium, 2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4, 5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butomethyl, 2,4,5-T-butyl, 2,4,5-T-butyl, 2,4, 5-T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl, 2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4, 5-T-sodium, 2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D, 2,4-D-2-butoxypropyl, 2,4-D-2- ethylhexyl, 2,4-D-3-butoxypropyl, 2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium, 2,4-DB-isoctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D-butyl, 2,4-D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium, 2, 4-D-diolamine, 2,4-D-dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl, 2,4-D-heptylamino, 2,4-Di sobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D-meptyl, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D-sodium, 2,4-D-tefuryl, 2, 4-D-tetradecylammonium, 2,4-D-triethylammonium, 2,4-D-tris (2-hydroxypropyl) ammonium, 2,4-D-trolamine, 2iP, 2-methoxyethylmercury chloride, 2-phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP, 4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPA-sodium, 4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol , 8-hydroxyquinoline sulfate, 8-phenylmercurioxiquinoline, abamectin, abscisic acid, ACC, acephate, acequinocyl, acetamipride, acetion, aceto-chlor, acetophos, acetoprol, acibenzolar, acibenzolar-S-methyl, acifluorphen-met, acifluorfen-acifluorfen-metifluorfen acifluorfen-sodium, aclonifen, acrep, acrinatrine, acrolein, acrylonitrile, acipetacs, acipetacs-copper, acipetacs-zinc, alachlor, alanicarb, albendazole, aldicarb, aldimorph, aldoxicarb, aldrin, alydrin, alydrin, aloxin, alydin sodium, allyl alcohol, alixi carb, aloraco, a / ta-cypermethrin, a / ta-endosulfan, ametocet-tradin, ametridione, ametrine, amibuzine, amicarbazone, amicartiazole, amidition, amidoflumete, amidosulfurone, aminocarb, aminocyclopyraclor, aminocyclopyraclor, aminocyclopyraclor, chlorinopyraclor aminopyralide, aminopyralide-potassium, aminopyralide-tris (2-hydroxypropyl) ammonium, amiprofos-methyl, amiprofos, amisulbrom, amiton, amiton oxalate, amitraz, amitrol, ammonium sulfamate, ammonium ammonium acetate, ammonium ammonium, ammonium ammonium, ampropane anabasin, ancimidol, anilazine, anilophos, anisuron, anthraquinone, antu, afolate, aramite, arsenous oxide, asomato, aspirin, asulam, asulam-potassium, asulam-sodium, atidation, atraton, atrazine, aureofungin, aviglicin , aviglycine hydrochloride, azaconazole, azadiractin, azafenidin, azametiphos, azinsulfurone, azinphos-ethyl, azinphos-methyl, aziprotrin, azitiram, azobenzene, azocyclotine, nitrogen, azoxystrobin, bachmedesh, barium, barium, barium, barium; rtrin, BCPC, beflubutamid, benalaxyl, benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin-ethyl, benazolin-potassium, bencarbazone, benclothiaz, bendio-carb, benfluralin, benfuracarb, benfures, benfurate, benfan, benfan, benfate benoxafos, benquinox, bensulfurone, bensulfuron-methyl, bensulide, bensultap, bentaluron, bentazone, bentazone-sodium, bentia- valicarb, bentiavalicarb-isopropyl, bentiazole, bentranyl, benzadox, benzadox-ammonium, benzmacryl-benzyl chloride isobutyl, benzamorf, benzfendizone, benzipram, benzobicyclon, benzofluor, benzofluor, benzohydroxamic acid, benzoximate, benzoilprop, benzoilprope-ethyl, benztiazuron, benzyl benzoate, benzyladenine, berberine, berberine chloride, beta-cifl , bicyclopyrone, biphenazate, bifenox, bifenthrin, bifujunzhi, bilanafos, sodium bilafos, binapacrila, bingqingxiao, bioalethrin, bioethanometrine, biopermetrin, bioresmethrin, biphenyl, bisazir, bismertiazole, bismertiazole ispiribac, bispiribac-sodium, bistrifluron, bitertanol, bitionol, bixafen, blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid, brassinolide, brassinoli- de-ethyl, brevicomin, brodifacoum, brofenvalerate, brofluthrinma, brofluthrinate, broma bromacil-sodium, bromadiolone, bromethalin, bromine, bromfenvinfos, bromoacetamide, bromobonil, bromobutide, bromocyclen, bromo-DDT, bromophenoxy, bromophos, bromofos-ethyl, bromopropylate, bromoxynil, bromoxynil, bromoxynil, bromoxynil, of bromoxynil, bromoxynil a-potassium, brompirazon, bromuconazole, bronopol, bucarpolate, bufencarb, buminaphos, bupyrimide, buprofezin, Burgundy mixture, busulfan, buta carb, butachlor, butafenacil, butamides, butamides, butamides, butamides, butamides, butamides , butiobate, buthiuron, butocarboxy, butonate, butopyronoxy, butoxycarboxy, butralin, butroxidim, buturon, butylamine, butylate, cacodylic acid, cadusaphos, cafenstrol, calcium arsenate, chlorate calcium, calcium cyanamide, calcium polysulfide, calvinfos, cambendichlor, campheclor, canfor, captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam, carbendazim, carbendazim benzenesulfonate, carbendazim sulfide, carbeturide, carbofuran, disulfide carbon, carbon tetrachloride, carbofenotion, carbosulfan, carboxazol, carboxide, carboxine, carfentrazone, carfentrazone-ethyl, carpropamide, cartap, cartap hydrochloride, carvacrol, carvone, CDEA, cellocidine, CEPC, ceralure, mixture Cheshunt, quinomethionat, chitosan, clobentiazone, clomethoxyfen, chloralose, chlorambene, chlorambenzammonium, chlorambene-diolamine, chloramben-methyl, chlorambenomethylammonium, chloramben-sodium, chloramine phosphorus, chloramphenicol, chlor-niformethane, chloramine, chloramine chlorazifop, chloro-zifop-propargyl, chlorazin, clorbenside, clorbenzuron, clorbicyclen, clorbromuron, chlorbufam, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, cl orempentrin, chlorethoxyfos, chloreturon, dorphenophen, chlorfenac-ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole, chlorfenetol, chlorfenprope, chlorfenson, chlorfensulfide, chlorfenvinfos, chlor-fluazuron, chlorflurazole, chlorfluren-chlorfluren methyl, chloridazon, chlorimuron, chlorimuron-ethyl, chlorephs, chlormequat, chlormequat chloride, chlornidine, chlornitrofen, chlorobenzylate, chlorodinitronaphthalenes, chloroform, chloromebuform, chloromethyluron, chloronebrine, chlorofacinone, chlorofin ropropylate, chlorothalon, chlorotoluron, chloroxurone, chloroxynil, chlorphonium, chlorphonium chloride, chlorfoxin, chlorprazophos, chlorprocarb, chlorpram, chlorpyrifos, chlorpyrifos-methyl, chlorquinox, chlorhloridone, clortyl, chlor-tal-dimetal chlortiamid, chlortiofos, clozolinate, choline chloride, chromafenozide, cinerin I, cinerin II, cinerines, cinidon-ethyl, cinmetiline, cinosulfurone, ciobutida, cisanilide , cismetrina, cleto-dim, climbazol, cliodinato, clodinafop, clodinafop-propargila, cloetocarb, clofencete, clofencete-potassium, clofentezine, clofibric acid, clofope, clofope-isobutyl, clomazone, clomeprope-clopropide, clopropid, clopropide, clopropide methyl, clopyralide-olamine, clopyralide-potassium, clopyralide-tris (2-hydroxypropyl) ammonium, cloquintocet, cloquintocet-mexila, chloransulam, chloransulam-methyl, closantel, clotianidine, clotri-mazol, cloxifonac, cloxifonacl, cloxifonacl colophonate, copper acetate, copper acetoarsenite, copper arsenate, copper carbonate, basic, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper silicate, copper sulfate, copper zinc chromate, cumaclor, cumafuril, cumafos, coumatetralila, coumitoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol, crimidine, crotamiton, crotoxifos, crufomate, cryolite, cue-lure, cufraneb, cumiluron, cuprobam, curdum, oxide cyanatrin, cyanozine, cyanophenphos, cyanophos, cyantoate, cyantraniliprol, cyanofamid, cybutin, cyclamide, cyclanilide, cyclethrin, cyclate, cycloheximide, cycloprate, cycloprotine, cyclosulfamuron, cyclohexidone, cycloxidine, cycloxidine cyfluthrin, cihalofop, cihalofop-butyl, cyhalothrin, cihexatin, cyimiazole, cyimiazole hydrocloride, cymoxanil, cytomethin, cyipendazole, cypermethrin, cyperquat, cyperquat chloride, cypressin, cyprazide, cyprazine, cyprazine, cyprazine, cyprazine prosulfamide, cyromazine, citioate, daimuron, dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide, dayoutong, dazomet, dazomet-sodium, DBCP, d-camphor, DCIP, DCPTA, DDT, debacarb, decafentin, decarbofuran, dehydroacetic acid, delaclor, deltamethrin, demefione, demefione-O, demefione-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, demon-ton-S -methylsulfon, desmedifam, desmetrina, d-fanshiluqu ebingjuzhi, diafentiuron, dialiphos, di-alate, diamidafos, diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate, dicamba, dicamba-diglycolamine, dicamba-dimethylammonium, dicamba-diolamine, dicamba-damba-isopropylamine , dicamba-potassium, dicamba-sodium, dicamba-trolamine, dicapton, diclobenyl, diclofention, diclofluanid, diclone, dichloralurea, diclorbenzuron, dichlorflurenol, dichloro-fluorol-methyl, dichloro-dichloro-dichloro-dichloro-dichloro, dichloro-dichloride , dichlorprope-butyl, dichlorprope-dimethylammonium, dichlorpro-pe-ethylammonium, dichlorprope-isoctyl, dichlorprope-methyl, dichlorprope-P, dichlorprope-P-2-ethylhexyl, dichlorprope-P-dimethylammonium, dichlorprope-dichlorprope, dichlorprope-dichlorprope , diclozoline, diclobutrazol, diclococimet, diclofope, diclofop-methyl, diclomezine, diclomezine-sodium, dichloran, diclosulam, dicofol, dicoumarol, dicresila, dicrotofos, dicycline, dicyclonon, dieldrin, dieldrin, dichrinchloride that of dietanquat, diethyl, diethyl-ethyl, dietofencarb, dietolate, diethyl pyrocarbonate, diethyltoluamide, difenacoum, diphenoconazole, diphenopentene, diphenopenten-ethyl, diphenoxuron, difenzoquat, difenzoquone methylene sulfate, difenzazone, difenzazone, difenzazone diflufenican, diflufenzopyr, diflu- fenzopyr-sodium, diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimeflutrin, dimefox, dimefurone, dimepiperate, dimethaclone, dimethane, dimetamethine, dimetamethine, dimetamethine, dimetamethine, dimetamethine, dimetamethine dimethoate, dimetomorph, dimethrin, dimethyl carbate, dimethyl phthalate, dimethylvinphos, dimethylan, dimexane, dimidazon, dimoxystrobin, dinex, dinex-diclexin, dingjunezuo, diniconazol, diniconazol-M, dinitocin, dinobuton, dinobuton, dinobuton, dinobuton, dinobuton, dinobuton, dinobuton, dinobuton, dinobuton, dinobuton, dinobuton, dinobutine dinocap-6, dinocton, dinofenate, dinopenton, dinoprope, dinosam, dinosebe, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium, dinoseb-trolamine, dinosulfon, dinotefuran, dinoter b, dino terb acetate, dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxation, di-facinone, diphacinone-sodium, diphenamid, diphenyl sulfone, diphenylamine, di-propalin, dipropetrin, dipyrithione, diquat, disiquul dibromide, disparlure, disparlure , disulfiram, disulfoton, disul-sodium, ditalimphos, dithianon, dichrophos, dithioeter, dithiopir, diuron, d-limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, dodemorph, dodephorus acetate , dodemorph benzoate, dodicin, dodicin hydrochloride, dodicine-sodium, dodine, dofenapin, dominicalure, doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdisterone, edifenfos, eglinazine, egli- nazine-ethylamine, and emamectin, EMPC, empentriin, endosulfan, endothal, endothal-diamonium, endothal-dipotassium, endothal-disodium, endothor, endrine, enestroburin, EPN, epocoleone, epophenonane, epoxiconazole, eprinomectin, epronaz, epronaz, epronaz, epronaz, epronaz, epronaz, epronazole, epronazole, epronazole, epronazole. , ergocalciferol, erlujixiancaoan, esdépaléthrina, esfenvalerato, esprocarb, eta- celasil, etaconazole, etafos, etem, etaboxam, etachlor, etalfluralin, ethametulfulfone, etametsulfuron-methyl, etaproclor, etefon, etidimuron, ethio-fencarb, etiolate, etion, etiozine, etiprol, etiofate, etirimol, etoexadiol, etoprofos, ethoxyfene, ethoxyfen-ethyl, ethoxyquin, ethoxysulfurone, ethylene oxide, ethyl formate, ethyl α-naphthalene acetate, ethyl-DDD, ethylene, ethyl dibromide, ethylene dichloride, ethylene oxide, ethylene oxide, ethylene oxide, ethylene oxide, ethylene oxide , 3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercury bromide, ethylmercury chloride, ethylmercury phosphate, ethinophene, etnipromid, etobenzanid, etofenprox, ethoxazole, etridiazole, etrinfid, phenoxyphenol, eulfenone, eugenol, fenamiphos, fenapanil, fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole, fenbutatin oxide, fenclorazol, fenclorazol-ethyl, fenclorfos, fenclorim, fenetacarb, fenflutrina, fenfuram, fenitrong enobucarb, fenenoprope, fenoprop-3-butoxypropyl, fenprope-butomethyl, fenprope-butyl, fenpropro-butyl, fenprope-isoctyl, fenprope-methyl, fenprop-potassium, fenotiocarb, fenoxacrim, fenoxanil, fenoxanil, phenoxanil fennoxaprope-P, fenoxaprope-P-ethyl, fenoxasulfone, fenoxicarb, fenpiclonil, fenpiritrina, fenpropatrina, fenpropidina, fenpropimorph, fenpirazaamina, fenpyoximate, fenridazon, fenridazon-potássio, fenridazon-propila, fenson, fenson, fenson, fenson, fenson, fenson, fenson, fenson, fenson, fenson, fenson, fensol, fensol, fensol, fenzen. fentiaprop, fentiaprope-ethyl, fention, fention-ethyl, fentin, fentin acetate, fentin chloride, fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA, fenfererate, ferbam, ferimzone, ferrous sulfate, fipron, flampron, flampron, flampron, flampron, flam- prope-isopropyl, flamprope-M, flamprope-methyl, flamprope-M-isopropyl, flamprope-M-methyl, flazasulfurone, flocoumafen, flonicamid, florasulam, fluacripirim, fluazifop, fluazifope-butyl, fluazifope-metila, fluazifope-metila fluazifop-P-butyl, fluazine m, fluazolate, fluazuron, flubendiamide, flubenzimine, flucarbazone, flucarbazone-sodium, fluceto-sulfurone, flucloralin, flucofurone, flucicloxuron, flucitrinate, fludioxonilla, fluenethyl, fluensulfone, flufoxoxen, flufoxoxen, flufenoxen, flufenoxen flufenpir, flufenpir-ethyl, flufiprol, flumetrin, flumetover, flumetralin, flumetsulam, flumezin, flumiclorac, flumiclorac-pentila, flumioxazin, flumipropin, flumorfo, fluometuron, fluopicolide, fluopiram, fluorofluorid, fluorofluorid, fluorofluorid fluoroimide, fluoromidine, fluoronitrofen, fluotiuron, fluotrimazole, fluoxastrobin, flupoxam, flupropacil, flupropadine, flupro-panate, flupropanate-sodium, flupirsulfuron, flupirsulfuron-methyl, flupir-sulfuron-methyl-flurur, fluolazole, fluolazol, fluolazol, fluolcon, fluolazol flurenol-methyl, fluridone, flurochloridone, fluroxypyr, fluroxypyr-butomethyl, fluroxypyr-meptila, flurprimidol, flursulamid, flurtamone, fl usilazole, flusulamide, flutiacete, flutiacete-methyl, flutianyl, flutolanil, flutriafol, fluvalinate, fluxpyroxade, fluxofenim, folpet, fomesafen, fomesafen-sodium, phonophos, foramsulfurone, forclorfenuron, formaldehyde, for- methanate, for- methanate, rhe- formotion, formparanate, formparanate hydrochloride, phosamine, phosamine-ammonium, fosetyl, fosetil-aluminio, fosmetilan, fospirate, fostiazate, fostietan, frontalin, fuberidazole, fucaojing, fucacomi, funaihecaoling, fufentiourea, furalano, furalano, furalano, furalano, furalano, furalano, furalano, furalano, furalano, furalano, furalano. furamethrin, furametpir, furatiocarb, furcarbanil, furconazole, furconazol-cis, furetrin, furfural, furilazole, furmeciclox, furofanate, furiloxifen, gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gibberellins, gliftor, glufosin, glufosin , glufosinate-P, glufosinate-P-ammonium, glufosinate-P- sodium, gliodin, glyoxime, glyphosate, glyphosate-diamonium, glyphosate-dimethylammonium, glyphosate-isopropylammonium, glyphosate-monoammon, glyphosate-potassium, glyphosate-potassium, glyphosate-potassium, glyphosate squisode, glyphosate-trimesium, glyphosine, gossiplure, grandlure, griseofulvin, guazatin, guazatin acetates, halakrinate, halfenprox, halofenozide, halosaphen, halosulfurone, ha-lossulfurone-methyl, haloxidine, haloxifox, haloxifop, haloxifope, haloxifope, haloxifope P, haloxifop-P-ethotyl, haloxifop-P-methyl, haloxypop-sodium, HCH, hemel, hempa, HEOD, heptachlor, heptenophos, heptopargil, heterophos, hexachloroacetone, hexachlorobenzene, hexachlorobutadiene, hexachloramine, hexachloramine hexaflumuron, hexaflurate, hexalure, hexamide, hexazinone, hexylthiophos, hexitiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo, hydramethylnon, hidrargafen, hydrated, hydrogen cyanide, hydroxy, hydroxy, hydroxy, hydroxy , imazalil nitrate, imazalil sulfate, imazametabenzo, imazametabenzo-methyl, imazamox, imazamox-ammonium, imazapic, imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, ima-zaquin, imazaquin-ammonium, imazaquin-ammonium, imazaquin-ammonium, mazaquin-sodium, imazetapyr, imazetapyr-ammonium, imazosulfurone, imibenconazole, imiciafos, imidacloprid, imidaclotiz, iminoctadine, iminoctadine triacetate, iminoctadine trial-iodine, iodine, indaminated, iodine, indifaminated, iodosulfurone, iodosulfurone-methyl, iodosulfurone-methyl-sodium, ioxynil, ioxinyl octanoate, ioxinyl-lithium, ioxynyl-sodium, ipazin, ipconazole, ipfencarbazone, iprobenfos, iprodione, iprovalam, isobenzan, isocarbamide, isocarbophos, isocyl, isodrine, isofenphos, isofenphos-methyl, isolan, isomethiozine, isonoruron, iso-polynate, isoprocarb, isopropalin, isoprothiolan, isoproturon, isopyrazone, isopyrone, isopyrolone, isopyrol, isoxaben, isoxaclortol, isoxadifene, isoxadifene-ethyl, isoxaflutol, isoxapyrifop, isoxathione, ivermectin, izopamfos, japonilure, japotrins, jasmine I, jasmine II, jasmineic acid o, jiahuangchongzong, jiajizengxiaolin, jia- xiangjunzhi, jiecaowan, jiecaoxi, jodfenfos, juvenile hormone I, juvenile hormone II, juvenile hormone III, cadetrin, carbutylate, caretazan, potassium potassium, casugamycin, kelamycin, hydrochloride, kalamycin, hydrochloride, kalaminic, hydrochloride, casamycin, hydrochloride, cetospiradox, cetospiradox-potassium, kinetin, cyinoprene, cresoxim-methyl, cuicaoxi, lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil, lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, lure, liture, liture Ivdingjunzhi, Ivxiancaolin, lytidation, MAA, malation, maleic hydrazide, malonobene, maltodextrin, MAMA, mancobre, mancozeb, mandipropamide, maneb, matrina, mazidox, MCPA, MCPA-2-ethylhexila, MCPA-butila, MCPA-butila, MCPA-butila, MCPA-butila , MCPA- dimethylammonium, MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPA-olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB , MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenyl, mecarbam, mecar-bin zida, mecarfon, mecoprop, mecoprope-2-ethylhexyl, mecoprope-dimethylammonium, mecoprope-diolamine, mecoprope-ethadyl, mecoprope-isoctyl, mecoprope-methyl, mecoprope-P, mecoprope-P-2-ethylhexyl, mecoprope-P-dimethylammon, mecoprope-P-isobutyl, mecoprope-potassium, mecoprope-P-potassium, mecoprope-sodium, mecoprope-trolamine, medimeform, medinoterb, medinoterb acetate, medlure, mefenacet, mefenpir, mefenpir-diethyl, mefluidide, mefluidide-diol, mefluidide-diol potassium, megatomoic acid, menazon, mepa-nipyrim, meperflutrin, mefenate, mefosfolan, mepiquat, mepiquat chloride, mepiquat pentaborate, mepronil, meptildinocape, mercuric chloride, mercuric oxide, mesosurone, mesosurone, meridian, sulfur, meridian -methyl, mesotrione, messulfen, messulfenphos, metaflumizone, metalaxyl, metalaxyl-M, metallohyde, metam, metam-ammonium, metamiphope, metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfurone, metazoxolon, metazoxolon, methazol, methazol, metepa zon, metabenztiazuron, methacrifos, metallopralin, metamidophos, metasulfocarb, metazol, metfuroxam, metidation, methiobencarb, metiocarb, methiopyrysulfurone, methiotep, methiozoline, methyron, metocrotofila, methomethoxy, methomethoxy, metheton, methomethoxy, metheton, methometho methoxychlor, methoxyfenozide, methoxyphenone, methyl afolate, methyl bromide, methyl eugenol, methyl iodide, methyl isothiocyanate, methyl acetofos, methyl chloroform, methyl dichloride, methylene chloride, methylmercury benzoate, dicarbonate, dicarbonate , methylneodecanamide, metiram, metobenzurone, metobromurone, metoflutrin, metolachlor, metolcarb, metominoestrobin, metosulam, methoxyzazone, methoxy-ron, metrafenone, metribuzin, metsulfovax, metsulfurone, metsulfurin-moss, myron-moss, methulfan-moss, methulfan-moss, methulfone-metholine , milneb, mipafox, mirex, MNAF, mogucun, molinate, molo-sultape, monalide, monisouron, monochloroacetic acid, mon ochrotophos, monolinuron, monosulfuron, monosulfuron-ester, monuron, mononuron TCA, morphanquat, morfamquat dichloride, moroxidine, moroxidine hydrochloride, morfotion, morzide, moxidectin, MSMA, musiclure, miclobanolin, ethylmercury) -p-toluenesulfonanilide, naam, naphthalophos, naled, naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyacetic acids, naproanilide, napropamide, naptalam, naphthalam-sodium, natamycin, nuramide, nuramide, neburonamide , nicotine, nifluridide, nipiraclofen, nitenpiram, nitiazine, nitralin, nitrapirin, nitrilacarb, nitrofen, nitrofluorfen, nitrosstyrene, nitralthaloprone, norbormide, norflurazon, nornicotine, noruron, novaluron, novalurone, ofura-, ometoate, orbencarb, orfralure, ortho-dichlorobenzene, ortosulfamuron, orictalure, orisastrobin, oryzine, ostol, ostramone, oxabetrinyl, oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxa pyrazon, oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfurone, oxaziclomefone, oxin-copper, oxolinic acid, oxpoconazole, oxpoconazole fumarate, oxycarboxine, oxide-methyl, oxideprofos, oxysulfoton, oxifluorine-chlorohydrate, oxymethacrine, oxytracycline , paclobu- trazol, paichongding, para-dichlorobenzene, parafluron, paraquat, paraquat dichloride, paraquat dimethyl sulfate, paration, paration-methyl, parinol, pebulate, pefurazoate, pelargonic acid, penconazol, penci- curon, pendimeten, penflureten, penfluren, penfluren penoxsulam, pentachlorophenol, pentanochlor, pentiopyrad, pentmetrine, pentoxazone, perfluidone, permethrin, petoxamide, fenamacril, phenazine oxide, phenisofam, fenencifam, fenmedifam-ethyl, phenobenzuron, phenothexide, phenoxyrene, phenotamine, pro phenylmercury, phenylmercury chloride, phenylmercury derivatives pyrocatechol, phenylmercury nitrate, phenylmercury salicylate, phorate, fosacetim, phosalone, fosdifeno, fosfolan, fosfolan-methyl, fosglicina, fosmet, fosniclor, fosfamidon, fosfina, fosfocarb, phosphorus, fostin, foxim, foxim-methyl, phthalide, picloram, picloram-2-ethylhexila, picloram-isoctila, picloram, picloram-isoctila, picloram pichloramolamine, pichloram-potassium, pichloram-triethylammonium, pichloram-tris (2-hydroxypropyl) ammonium, picolinafen, picoxystrobin, pindone, pindona-sodium, pinoxaden, piperalin, piperonyl butoxide, piperonyl cyclonene, piperofyl, piperofyl, piperophyll , piprotal, pyrimetafos, pyrimicarb, pyrimioxifos, pyrimiphos-ethyl, pyrimiphos-methyl, plifenate, poly-carbamate, polyoxins, polyoxorin, polixorim-zinc, politialan, potassium arsenite, azide potassium, potassium cyanate, potassium cyanate, gibberelate potassium, potassium polysulfide, potassium thiocyanate, potassium α-naphthaleneacetate, pp'-DDT, pralethrin, precocene I, precocene II, precocene III, pretilachlor, primidofos, primisulfurone, primisulfurone-methyl, probenazole, prochloraz, prochloraz loraz-manganese, proclonol, prociazine, procymidone, prodiamine, profenofos, profluazole, profluralin, proflutrin, profoxidim, proglinazine, proglinazine-ethyl, proexadione, proexadione-calcium, proidrojasmon, promacila, pro-carb, promethit, prometon, promethit, promethine, promethin, promethine, promethine propamidine, propamidine dihydrochloride, propamocarb, propamocarb hydrochloride, propanil, propafos, propaquizafope, propargite, propartrine, propazine, propetamfos, profam, propiconazole, propineb, propisochlor, propoxur, propoxicarbazone, propoxicarbazone, propoxyazone , propizamide, proquinazide, prosuler, prosulfalin, prosulfocarb, prosulfurone, protidation, protiocarb, protiocarb hydrochloride, protioco-nazol, protiofos, protoate, protrifenbuto, proxan, proxan-sodium, prine-chlor, pidanon, pyrethylamine, piracl, piracl, piracl , piraclostrobin, piraflufen, piraflufen-ethyl, pirafluprol, piramat, pirametostrobin, piraoxystrobin, pyrasulfotol, pyrazolinate, pyraz ofos, pyrazosulfurone, pyrazosulfurone-ethyl, pyrazothion, pyrazoxifene, pyrethrine, pyrethrin I, pyrethrin II, pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb, pyribenzoxim, pyributicarb, pyrichloride, pyridine, pyridine, pyridine, pyridine, pyridine pyridafention, pyridate, pyridinitrile, pyrifenox, pyrifluquinazon, pyriftalide, pyrimethanil, pyrimidifene, pyriminobac, pyriminobacmethyl, pyrimisulfan, pyrimitate, pyrinuron, pyrophenone, pyriprol, pyripro-pyrol, pyropyrol, pyropyrol, pyripyrol, pyripyrol, pyripyrol, pyripyrol, pyropyrol, pyridine pyroxasulfone, pyroxsulam, pyroxychlor, pyroxifur, quassia, quinacetol, quinacetol sulphate, quinalfos, quinalfos-methyl, quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine, quinonamide, quinotion, quino-xeno, quino-quino-quino-quino-quino-quino-quizofino ethyl, quiza-lofope-P, quizalofope-P-ethyl, quizalofope-P-tefuril, quwenzhi, quyingding, rabenzazole, rafoxanide, rebemida, resmetrina, rodetanil, rodojaponina-lll, ribavir ina, rinsulfurone, rote nona, riânia, saflufenacil, saijunmao, saisentong, salicilanilida, sanguinarina, santonina, schra- dan, escilirosida, sebutilazine, seebumeton, silkxane, selamectin, semiamitraz, semiamitraz chloride, siamitrazetoxam, siamexamines, saminametam, siamexamines, , siglure, silafluofen, silatrano, silica gel, siliofam, simazine, simeconazole, simeton, simetrina, sintofen, SMA, S- metolachlor, sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodium fluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodium orthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide, sodium thiocyanate, sodium α-naphthaleneacetate, sofamide, espinetoram, spinosad, spirodiclofen, spiromesifene, spyrothemato, spyrotetraamine, spyrotetraamine strepto-mycine sesquisulfate, strychnine, sulcatol, sulcofurone, sulcofuron-sodium, sulcotrione, sulfalate, sulfentrazone, sulfiram, sulfluramide, sulfometuron, sulfometuron-methyl, su lphosulfurone, sulfotep, sulfoxaflor, sulfoxide, sulfoxide, sulfur, sulfuric acid, sulfuryl fluoride, sulglicapin, sulprofos, sultropen, swep, tau-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA-calcium, TCA-ethyl , TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide, tebufenpirad, tebufloquin, tebupirimphos, tebutam, tebutiuron, keyboardophthalam, teflutrin, teflutrin, temfur, tefltrone and temefe , teraletrine, terbacil, terbucarb, terbuclor, terbufos, terbumeton, terbutilazine, terbutrin, tetciclacis, tetrachloroethane, tetrachlorvinphos, tetraconazole, te- tradifon, tetrafluron, tetramethin, tetramethyl, tetramethyl, tetramethyl, tetramethyl, tetramethyl -cipermethrin, thiabendazole, thiaclopride, thiadifluor, thiametoxam, tiapronil, tiazafluron, tiazopir, ticro-fos, ticiofen, tidiazimin, tidiazuron, tiencarbazone, tiencarbazone-methyl, tifensulfurone, tifensulfurone, tifensulfurone, tifensulfurone, tifensulfurone, tifensulfurone, tifensulfurone, tifensulfurone, tifensulfuron bencarb, thio-carboxime, thioclorfenfim, thiocyclam, thiocyclam hydrochloride, thioclam oxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoxime, thioempa, thiomersal, thiometon, thionazine, thiophanate, thiophanate-thioquinone, thioquinoxide, thioquinoxide, thioquino- thiosultap-diamonium, thiosultap-disodium, thiosulphate-monosodium, thiotepa, tiram, turingiensin, thiadinyl, tiaojiean, tiocarbazil, tioclorim, thioximid, tirpate, tolclofos-methyl, tolfenpirad, tolylfluanide, trilyloxyacetone, tolylmercury, tolylamine tralocitrin, tralo-metrin, tralopyril, transflutrina, transpermetrina, tretamina, triacontanol, triadimefon, triadimenol, triafamona, tri-alato, triamifos, triapentenol, triarateno, triarimol, triasulfurone, triaza, triazine, triazine, triazine methyl, tribufos, tributyltin oxide, tricamba, triclamide, triclorfon, triclormetafos-3, trichloro-nat, triclopir, triclopyr-butyl, triclopir-ethyl, triclopir-trietilamônio, triclopyr icichlazole, tridemorph, tridiphane, trietazine, triphenmorph, triphenophos, trifloxystrobin, trifloxysulfurone, trifloxysulfuron-sodium, triflumizol, triflumuron, trifluralin, triflusulfuron, triflifine, trifloxin, trifltrine trimetacarb, trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan, triptolide, tritac, triti- conazole, tritosulfurone, trunc-lime, uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin, valifenalate, valifenalate, valifenalate, valifenalate, valifenalate, valifenalate, vaniliprol, vernolate, vinclozoline, warfarin, warfarin potassium, warfarin sodium, xiaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols, xylilcarb, yishijing, zarilamide, zeatin, zengincooanetam, zeta zincoxymethyl, zeta zinc, zi-nebe, ziram, zolaprofos, zoxamide, zuomihuanglong, α-chlorohydrin, α-ecdysone, α-multistriatin, and α-naphthalene acetic acid. For more information, see the “Compendium of Pesticide Common Names” located at http://www.alanwood.net/pesticides/index.html. Also see “Te Pesticide Manual” 14th Edition, edited by CDS Tomlin, copiright 2006 by British Crop Production Council, or its previous or most recent editions. BIOPESTICIDES
[00249] Formula One molecules can also be used in combination (such as in a compositional mix, or simultaneous or sequential application) with or more biopesticides. The term "biopesticide" is used for biological microbial pest control agents which are applied in a similar way to chemical pesticides. These are commonly bacterial, but there are also examples of fungal control agents, including Trichodermaspp. and Ampelomyces quisqualis (a control agent for grape powdery mold). Bacillus subtilis are used to control plant pathogens. Weeds and rodents were also controlled with microbial agents. An example of a well-known insecticide is Bacillus thuringiensis, a bacterial disease of Lepidoptera, Coleoptera, and Diptera. Because it has a small effect on other organisms, it is considered more pleasant to the environment than synthetic pesticides. Biological insecticides include products based on:
[00250] entomopathogenic fungi (for example, Metarhizium anisopliae) ',
[00251] entomopathogenic nematodes (eg Steinernema feltiae) ', and
[00252] entomopathogenic viruses (for example, Cidia pomonella granulovirus).
[00253] Other examples of entomopathogenic organisms include, but are not limited to, baculoviruses, bacteria and other prokaryotic organisms, fungi, protozoa and Microsproridia. Biologically derived insecticides include, but are not limited to, rotenone, veratridine, as well as microbial toxins; varieties of plants resistant or tolerant to insects; and organisms modified by recombinant DNA technology to produce insecticides or impart an insect-resistant property to the genetically modified organism. In one embodiment, Formula One molecules can be used with one or more biopesticides in the field of seed treatment and soil improvement. The Manual of Bio-control Agents provides a review of the available biological insecticide products (and other biology-based control products). Copping L.G. (ed.) (2004). The Manual of Biocontrol Agents (formerly te Biopesticide Manual) 3rd Edition. British Crop Production Council (BCPC), Farnham, Surrey UK. OTHER ACTIVE COMPOUNDS
[00254] Formula One molecules can also be used in combination (such as in a compositional mix, or simultaneous or sequential application) with one or more of the following:
[00255] 3- (4-chloro-2,6-dimethylphenyl) -4-hydroxy-8-oxa-1 - azospiro [4,5] dec-3-en-2-one;
[00256] 3- (4'-chloro-2,4-dimethyl [1,1'-biphenyl] -3-yl) -4-hydroxy-8-oxa-1-azospiro [4,5] dec-3- en-2-one;
[00257] 4 - [[(6-chloro-3-pyridinyl) methyl] methylamino] -2 (5H) -furanone;
[00258] 4 - [[(6-chloro-3-pyridinyl) methyl] cyclopropylamino] -2 (5H) - furanone;
[00259] 3-chloro-A / 2 - [(1 S) -1-methyl I -2- (methyl Ifoni I) ethyl] -A / 1 - [2-methyl-4- [1,2,2, 2-tetrafluoro-1 - (trifluoromethyl) ethyl] phenyl] -1,2-benzenodicarboxamide;
[00260] 2-cyano-A / -ethyl-4-fluor-3-methoxy-benenesulfonamide;
[00261] 2-cyano-A / -ethyl-3-methoxy-benzenesulfonamide;
[00262] 2-cyano-3-difluoromethoxy-A / -ethyl-4-fluoro-benzenesulfonamide;
[00263] 2-cyano-3-fluoromethoxy-A / -ethyl-benzenesulfonamide;
[00264] 2-cyano-6-fluoro-3-methoxy-A /, A / -dimethyl-benzenesulfonamide;
[00265] 2-cyano- / V-ethyl-6-fluoro-3-methoxy-A / -methyl-benzenesulfonamide;
[00266] 2-cyano-3-difluoromethoxy-A /, A / -dimethylbenzenesulfon-amide;
[00267] 3- (difluoromethyl) -A / - [2- (3,3-dimethylbutyl) phenyl] -1-methyl-1H-pyrazol-4-carboxamide;
[00268] A / -ethyl-2,2-dimethylpropionamide-2- (2,6-dichloro-a, a, a-trifluor-p-tolyl) hydrazone;
[00269] A / -ethyl-2,2-dichloro-1-methylcyclopropano-carboxamide-2- (2,6-dichloro-a, a, a-trifluoro-p-tolyl) hydrazone nicotine;
[00270] O - {(E -) - [2- (4-chloro-phenyl) -2-cyano-1- (2-trifluoromethylphenyl) -vinyl]} thiocarbonate]} S-methyl;
[00271] (E) -N1 - [(2-chloro-1,3-thiazol-5-ylmethyl)] - N2-cyano-N1-methylacetamidine;
[00272] 1 - (6-chloropyridin-3-ylmethyl) -7-methyl-8-nitro-1,2,3,5,6,7-hexahydro-imidazo [1,2-a] pyridin-5-ol ;
[00273] 4- [4-chlorophenyl- (2-butylidine-hydrazono) methyl)] phenyl mesylate; and
[00274] N-Ethyl-2,2-dichloro-1-methylcyclopropanecarboxamide-2- (2,6-d chloro-a / fa, alpha, a / fa-trifluor-p-tol i I) h i d razone. SYNERGISTIC MIXTURES
[00275] Formula One molecules can be used with certain active compounds to form synergistic mixtures where the method of action of such compounds compared to the method of action of Formula One molecules are the same, similar, or different. Examples of methods of action include, but are not limited to: acetylcholinesterase inhibitor; sodium channel modulator; chitin biosynthesis inhibitor; passage chloride channel antagonist by means of GABA and glutamate; agonist of the chloride channel through GABA and glutamate; acetylcholine receptor agonist; acetylcholine receptor antagonist; MET I inhibitor; Mg-stimulated ATPase inhibitor; nicotinic acetylcholine receptor; rupture of the midgut membrane; disruptive of oxidative phosphorylation, and ryanodine receptor (RyRs). Generally, the weight ratios of the Formula One molecules in a synergistic mixture with another compound are from about 10: 1 to about 1:10, in another embodiment from about 5: 1 to about 1: 5, and in another mode of about 3: 1, and in another mode about 1: 1. FORMULATIONS
[00276] A pesticide is rarely suitable for application in its pure form. It is usually necessary to add other substances so that the pesticide can be used in the required concentration and in an appropriate form, allowing ease of application, handling, transportation, storage, and maximum pesticidal activity. In this way, pesticides are formulated in, for example, baits, concentrated emulsions, powders (dusts), emulsifiable, steaming concentrates, gels, granules, microencapsulations, seed treatment, suspension concentrates, suspoemulsions, tablets, water-soluble liquids, water-dispersible or dry-flowing granules, wetting powders, and ultra-low volume solutions. For further information on types of formulations see “Catalog of Pesticide Formulation Types and International Coding System” Technical Monograph n ° 2, 5th Edition by CropLife International (2002).
[00277] Pesticides are most often applied as aqueous emulsions or suspensions prepared from concentrated formulations of such pesticides. Such water-soluble, water-suspendable or emulsifiable formulations are solid, commonly known as wetting powders, or water-dispersible granules, or liquids commonly known as emulsifiable concentrates, or aqueous suspensions. The wetting powders, which can be compacted to form water-dispersible granules, comprise an intimate mixture of the pesticide, a carrier, and surfactants. The concentration of the pesticide is usually about 10% to about 90% by weight. The vehicle is usually selected from atapulgite clays, montmorillonite clays, diatomaceous earth, or purified silicates. Effective surfactants, comprising from about 0.5% to about 10% of the wetting powder, are found among sulfonated lignins, condensed naphthalenesulfonates, naphthalenesulfonates, alkylbenzenesulfonates, alkyl sulfates, and non-ionic surfactants such as adducts of ethylene oxide from alkyl phenols.
[00278] Pesticide emulsifiable concentrates comprise a convenient concentration of a pesticide, such as from about 50 to about 500 grams per liter of liquid dissolved in a vehicle that is a water-miscible solvent or a mixture of emulsifiers and water-immiscible organic solvent. Useful organic solvents include aromatics, especially xylenes and oil fractions, especially the high boiling olefinic and naphthalene portions of oil such as heavy aromatic naphtha. Other organic solvents can also be employed, such as terpenic solvents including rosin derivatives, aliphatic ketones such as cyclohexanone, and complex alcohols such as 2-ethoxyethanol. Emulsifiers suitable for emulsifiable concentrates are selected from conventional anionic and non-ionic surfactants.
[00279] Aqueous suspensions comprise suspensions of water-insoluble pesticides dispersed in an aqueous vehicle at a concentration in the range of about 5% to about 50% by weight. The suspensions are prepared by finely grinding the pesticide and mixing vigorously in a vehicle comprised of water and surfactants. Ingredients such as inorganic and synthetic salts or natural gums can also be added to increase the density and viscosity of the aqueous vehicle. It is often more effective to grind and mix the pesticide at the same time by preparing the aqueous mixture and homogenizing it in an implement such as a sand mill, ball mill or piston-type homogenizer.
[00280] Pesticides can also be applied as granular compositions that are particularly useful for soil applications. Granular compositions typically contain from about 0.5% to about 10% by weight of the pesticide, dispersed in a vehicle comprising clay or a similar substance. Such compositions are usually prepared by dissolving the pesticide in a suitable solvent and applying it to a granular carrier that has been preformed in the appropriate particle size, in the range of about 0.5 to about 3 mm. Such compositions can also be formulated by preparing a carrier or compound paste or mass and crushing and drying to obtain the desired granular particle size.
[00281] Powders containing a pesticide are prepared by intimately mixing the pesticide in powder form with a suitable dusty farming vehicle, such as kaolin clay, ground volcanic stone, and the like (s). The powders can suitably contain from about 1% to about 10% of the pesticide. They can be applied as a seed fertilizer or as a foliage application with a powder blowing machine.
[00282] It is also practical to apply a pesticide in the form of a solution in an appropriate organic solvent, usually petroleum oil, such as spray oils, which are widely used in agricultural chemistry.
[00283] Pesticides can also be applied in the form of an aerosol composition. In such compositions the pesticide is dissolved or dispersed in a vehicle, which is a mixture of propellant generating pressure. The aerosol composition is packaged in a container from which the mixture is dispensed via a spray valve.
[00284] Pesticide baits are formed when the pesticide is mixed with food or an attractant or both. When pests eat the bait they also consume the pesticide. The baits can take the form of granules, gels, flowable powders, liquids, or solids. They can be used in pest shelters.
[00285] Fumigants are pesticides that have a relatively high vapor pressure and thus can exist as a gas in sufficient concentrations to kill pests indoors or on the ground. The toxicity of the fumigant is proportional to its concentration and the time of exposure. They are characterized by a good diffusion capacity and act by penetrating the plague's respiratory system or being absorbed through the plague's cuticle. The steamers are applied to control pests of products stored under gas-proof sheets, indoors or in buildings or in special chambers.
[00286] Pesticides can be microencapsulated by suspending drops or particles of pesticide in plastic polymers of various types. By changing the polymer chemistry or changing factors in processing, microcapsules can be formed of various sizes, solubility, wall thicknesses, and degrees of penetrability. These factors regulate the speed at which the active ingredient is released, which also affects the residual performance, the speed of action, and the odor of the product.
[00287] Oily solution concentrates are made by dissolving the pesticide in a solvent that will keep the pesticide in solution. The oily solutions of a pesticide usually provide the death and faster reduction of pests than other formulations due to the solvents themselves having pesticidal action and the dissolution of the waxy coating of the integument increasing the speed of uptake of the pesticide. Other advantages of oily solutions include better storage stability, better penetration into cracks, and better adhesion to oily surfaces.
[00288] Another embodiment is an oil-in-water emulsion, in which the emulsion comprises oily globules which are each provided with a lamellar liquid crystal coating and are dispersed in an aqueous phase, in which each oily globule comprises at least a compound that is agriculturally active, and is individually coated with a monolamellar or oligolamellar layer comprising: (1) at least one nonionic lipophilic surfactant, (2) at least one nonionic hydrophilic surfactant and (3) at least an ionic surfactant, in which blood cells having an average particle diameter of less than 800 nanometers. Further information on the modality is described in United States Patent Publication 20070027034 published on February 1, 2007, with Patent Application number 11 / 495,228. For ease of use, this modality will be referred to as “OIWE”.
[00289] For further information, see “Insect Pest Management” 2nd Edition by D. Dent, copiright CAB International (2000). In addition, for more details see “Handbook of Pest Control - The Behavior, Life History, and Control of Household Pests” by Arnold Malis, 9th Edition, copiright 2004 by GIE Media Inc. OTHER FORMULATION COMPONENTS
[00290] Generally, when the molecules described in Formula One are used in a formulation, such formulation may also contain other components. These components include, but are not limited to, (this is a non-mutually exclusive and non-exhaustive list) humectants, extenders, thickeners, penetrants, tampons, sequestering agents, swirl reducing agents, compatibility agents, agents anti-foam, cleaning agents, and emulsifiers. Some components are described immediately.
[00291] A wetting agent is a substance that when added to a liquid increases the extent or penetration of powder in the liquid, reducing the interfacial tension between the liquid and the surface on which it is propagated. Wetting agents are used for two main functions in agrochemical formulations: during processing and manufacturing to increase the rate of wetting of powders in water to prepare concentrates for soluble liquids or suspension concentrates; and during mixing a product with water in a vaporization tank to reduce the wetting time of wetting powders and to improve water penetration into water-dispersible granules. Examples of wetting agents used in wetting powder, suspension concentrate and water-dispersible granule formulations are: sodium lauryl sulfate; sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and ethoxylates of aliphatic alcohol.
[00292] A dispersing agent is a substance that absorbs on the surface of particles and helps to preserve the dispersion state of the particles and prevents them from regrouping. Dispersing agents are added to agrochemical formulations to facilitate dispersion and suspension during manufacture, and to ensure particles redispersed in the water in a spray tank. They are widely used in wetting powders, suspension concentrates and water-dispersible granules. Surfactants that are used as dispersing agents have the ability to absorb strongly on a particle surface and provide a sterile or charged barrier for the re-aggregation of particles. The most commonly used surfactants are anionic, non-ionic, or mixtures of the two types. For wettable powder formulations, the most common dispersing agents are sodium lignosulfonates. For suspension concentrates, stabilization and very good absorption are achieved by using polyelectrolytes, such as condensates from sodium naphthalene sulphonate formaldehyde. Tristyrylphenol ethoxylated phosphate esters are also used. Nonionics such as alkylaryl ethylene oxide condensates and EO-PO blocking copolymers are sometimes combined with anionics as dispersing agents for suspension concentrates. In recent years, new types of very high molecular weight polymeric surfactants have been developed as dispersing agents. These have very long hydrophobic 'main chains' and a large number of ethylene oxide chains forming the 'teeth' of a 'comb' surfactant. These high molecular weight polymers can provide very good long-term stability to the suspension concentrates because the hydrophobic main chains have many anchor points on the particle surfaces. Examples of dispersing agents used in agrochemical formulations are: sodium lignosulfonates; condensates of sodium naphthalene sulfonate formaldehyde; ethoxylated phosphate esters of tristyrylphenol; ethoxylates of aliphatic alcohol; alkyl ethoxylates; EO-PO block copolymers; and graft copolymers.
[00293] An emulsifying agent is a substance that stabilizes a suspension of drops from one liquid phase to another liquid phase. Without the emulsifying agent the two liquids would separate into two immiscible liquid phases. The emulsifying mixtures most commonly used contain alkylphenol or aliphatic alcohol with twelve or more units of ethylene oxide and the calcium salt soluble in oil of dodecylbenzenesulfonic acid. A range of hydrophilic-lipophilic (“HLB”) equilibrium values from 8 to 18 will normally provide very stable emulsions. Emulsion stability can sometimes be improved by adding a small amount of an EO-PO blocking copolymer surfactant.
[00294] A solubilizing agent is a surfactant that will form mice in water at concentrations above the critical micelle concentration. The micelles are therefore capable of dissolving or solubilizing the water-insoluble materials within the hydrophobic part of the micelle. The types of surfactants normally used for solubilization are non-ionic, sorbitan monooleates, sorbitan monooleate ethoxylates, and methyl oleate esters.
[00295] Surfactants are sometimes used, alone or with other additives such as mineral or vegetable oils as adjuvants for tank mixtures to improve the biological performance of the pesticide on the target. The types of surfactants used for bioreactor generally depend on the nature and method of action of the pesticide. However, they are often non-ionic such as: alkyl ethoxylates; linear aliphatic alcohol ethoxylates; aliphatic amine ethoxylates.
[00296] A vehicle or diluent in an agricultural formulation is a material added to the pesticide to provide a product of the required strength. Vehicles are usually materials with high absorptive capacities, while thinners are usually materials with low absorptive capacities. Vehicles and diluents are used in the formulation of powders, wetting powders, granules and granules dispersible in water.
[00297] Organic solvents are mainly used in the formulation of emulsifiable concentrates, oil-in-water emulsions, suspoemulsions and ultra low volume formulations, and to a lesser extent, granular formulations. Sometimes solvent mixtures are used. The first major groups of solvents are aliphatic paraffinic oils such as kerosene or refined paraffins. The second main group (and the most common) comprises aromatic solvents such as xylene and higher molecular weight fractions of C9 and C10 aromatic solvents. Chlorinated hydrocarbons are useful as cosolvents to prevent crystallization of pesticides when the formulation is emulsified in water. Alcohols are sometimes used as cosolvents to increase the power of the solvent. Other solvents may include vegetable oils, seed oils, and esters of vegetable and seed oils.
[00298] Thickeners or gelling agents are used mainly in the formulation of suspension concentrates, emulsions and suspoemulsions to modify the rheology or flow properties of the liquid and to prevent the separation and sedimentation of the dispersed drops or particles. Thickeners, gelling and anti-sedimentation agents fall into two categories, namely: water-insoluble particles and water-soluble polymers. It is possible to produce suspension concentrate formulations using clays and silica. Examples of these types of materials include, but are not limited to, montmorillonite, bentonite, magnesium aluminum silicate, and atapulgite. Water-soluble polysaccharides have been used as thickening-gelling agents for many years. The types of polysaccharides most commonly used are natural extracts of seeds and algae or are synthetic cellulose derivatives. Examples of these types of materials include, but are not limited to, guar gum; locust bean gum; carrageenan; algae; methyl cellulose; sodium carboxymethyl cellulose (SCMC); hydroxyethyl cellulose (HEC). Other types of anti-sedimentation agents are based on modified starches, polyacrylates, polyvinyl alcohol and polyethylene oxide. Another good anti-sedimentation agent is xanthan gum.
[00299] Microorganisms can cause waste of formulated products. Therefore, preservation agents are employed to eliminate or reduce its effects. Examples of such agents include, but are not limited to: propionic acid and its sodium salt; sorbic acid and its sodium or potassium salts; benzoic acid and its sodium salt; sodium salt of p-hydroxybenzoic acid; methyl p-hydroxybenzoate; and 1,2-benzisothiazolin-3-one (BIT).
[00300] The presence of surfactants often leads to water-based formulations to foam during mixing operations in production and application through a vaporization tank. In order to reduce tendencies to foam, defoaming agents are often added during the production stage or before loading into bottles. There are generally two types of antifoam agents, namely: silicones and non-silicones. Silicones are usually aqueous emulsions of dimethyl polysiloxane, while non-silicone antifoam agents are water-insoluble oils, such as octanol and nonanol, or silica. In both cases, the function of the defoamer is to detach the surfactant from the air-water interface.
[00301] "Green" agents (for example, adjuvants, surfactants, solvents) can reduce the total environmental footprint of crop protection formulations. Green agents are biodegradable and generally derived from natural and / or sustainable sources, for example, plant and animal sources. Specific examples are: vegetable oils, seed oils, and esters of these, also alkoxylated alkyl polyglucosides.
[00302] For further information, see "Chemistry and Technology of Agrochemical Formulations" edited by D.A. Knowles, copiright 1998 by Kluwer Academic Publishers. See also "Insecticides in Agriculture and Environment - Retrospects and Prospects" by A.S. Perry, I. Yamamoto, I. Ishaaya, and R. Perry, copiright 1998 by Springer-Verlag. PESTES
[00303] In general, Formula One molecules can be used to control pests, for example, beetles, water rats, cockroaches, flies, aphids, scales, white flies, leafhoppers, ants, wasps, termites, moths, butterflies, lice, grasshoppers, cicadas, crickets, fleas, thrips, moths, mites, ticks, nematodes, and symphylates.
[00304] In another embodiment, Formula One molecules can be used to control pests in Phyla Nematoda and / or Arthropoda.
[00305] In another embodiment, Formula One molecules can be used to control pests in Subphyla Chelicerata, Myriapoda, and / or Hexapoda.
[00306] In another embodiment, Formula One molecules can be used to control pests in the classes of Arachnida, Symphyla, and / or Insecta.
[00307] In another embodiment, Formula One molecules can be used to control pests of the Anoplura Order. A non-exhaustive list of particular genera includes, but is not limited to, Haematopinus spp., Hoplopleura spp., Linognathus spp., Pediculus spp., And Polyplax spp. A non-exhaustive list of particular species includes, but is not limited to, Haematopinus asini, Haematopinus suis, Linognathus setosus, Linognathus ovillus, Pediculus humanus capitis, Pediculus humanus humanus, and Ptirus pubis.
[00308] In another embodiment, Formula One molecules can be used to control pests in the Order Coleoptera. A non-exhaustive list of particular genera includes, but is not limited to, Acanthoscelides spp., Agriotes spp., Antonomus spp., Apion spp., Apogonia spp., Aulacophora spp., Bruchus spp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp., Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp., Cyclocephala spp., Diabrotica spp., Hypera spp., Ips spp., Lyctus spp., Megascelis spp. spp., Otiorhynchus spp., Pantomorus spp., Phyllophaga spp., Phyllotreta spp., Rhizotrogus spp., Rhynchites spp., Rhynchophorus spp., Scolytus spp., Sfenopho-rus spp., Sitophilus spp., and Tribol A non-exhaustive list of particular species includes, but is not limited to, Acantoscelides obtectus, Agrilus planipennis, Anoplophora glabripennis, Antonomus grandis, Ataenius spretulus, Atomaria linearis, Bothynoderes puncti- ventris, Bruchus pisorum, Ca osobruchus maculatus, Carpophilus he- m , Cassida vittata, Cerotoma trifurcata, Ceutorhynchus assimi- lis, Ceutorhynchus napi, Conoderus scalaris, Conoderus stigmosus, Conotrachelus nenuphar, Cotinis nitida, Crioceris asparagi, Cryptolises ferrugineus, Criptolestes pusillus- turis- lardarius, Dermesentes maculatus, Epilachna varivestis, Faustinus cubae, Hylobius pales, Hypera false, Hypotenemus hampei, Lasioderma serricorne, Lepti- notarsa decemlineata, Liogenys fuscus, Liogenys suturalis, Lissorhopi trisy Melolonta melolonta, Oberea brevis, Oberea linearis, Oryctes rhinoc eros, Oryzaephilus mercator, Oryzaephilus surinamensis, Oulema melanopus, Oulema oryzae, Phyllophaga cuyabana, Popillia japonica, Prostephanus truncatus, Rhyzoperta dominica, Sitona lineatus, Sitophilus granarius, Sitophilus castan, Sitophilus cast, zoophile , Trogoderma variabile, and Zabrus tenebrioides.
[00309] In another embodiment, Formula One molecules can be used to control pests of the Dermaptera Order.
[00310] In another embodiment, the Formula One molecules can be used to control pests of the Blattaria Order. A non-exhaustive list of particular species includes, but is not limited to, Blattella germanica, Blatta orientalis, Parcoblatta pennsylvanica, American periplaneta, Periplaneta australasiae, Periplaneta brunnea, Periplaneta fuliginosa, Pycnoscelus surinamensis, and Supella longipalpa.
[00311] In another embodiment, the Formula One molecules can be used to control pests of the Order Diptera. A non-exhaustive list of particular genera includes, but is not limited to, Aedesspp., Agromyza spp., Anastrepha spp., Anophelesspp., Bactro-cera spp., Ceratitis spp., Chrysops spp., Cochliomyia spp., Contarinia spp. , Culex spp., Dasineura spp., Delia spp., Drosophilaspp., Fannia spp., Hylemyia spp., Liriomyza spp., Muscaspp., Phorbia spp., Tapanus spp., And Tipula spp. A non-exhaustive list of particular species includes, but is not limited to, Agromyza frontella, Suspended Anastrepha, Anastrepha ludens, Anastrepha obliqa, Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera invadens, Bactrocera zonata, Ceratitis capitata, Dasineura plicaura, Delineia brassicae Fannia canicularis, Fannia scalaris, Gasterophilus intestinal is, Gracillia perseae, Haematobia irritans, Hypoderma lineatum, Liriomyza brassicae, Melophagus ovinus, Musca autumnal is, Musca domestica, Oestrus ovis, Oscinella frit, Pegomya betae, Pshagis cere pomoonella, Rhagoletis mendax, Sitodiplosis mosellana, and Stomoxis calcis.
[00312] In another embodiment, Formula One molecules can be used to control pests of the Hemiptera Order. A non-exhaustive list of particular genera includes, but is not limited to, Adelges spp., Aulacaspis spp., Aphrophoraspp., Aphisspp., Bemisispp., Ceroplastes spp., Chionaspis spp., Chrysomphalus spp., Coccus spp., Empoasca spp., Lepidosaphes spp., Lagynotomus spp., Lygus spp., Macrosiphum spp., Nephotettix spp., Nezara spp., Philaeus spp., Phytocoris spp., Piezodorus spp., Pianococcus spp., Pianococcus spp. Rhopalosiphum spp., Saissetia spp., Terioaphis spp., Toumeyella spp., Toxoptera spp., Trialeurodes spp., Triatoma spp. and Unaspis spp. A non-exhaustive list of particular species includes, but is not limited to, Acrosternum hilare, Acirtosiphon pisum, Aleyrodes proletella, Aleurodicus dispersus, Aleurothrixus floccosus, Amrasca biguttula biguttula, Aonidiella aurantii, Aphis gossypii, Aphis glycinas, Aphis pumani ,ul argentifolii, Bemisia tabaci, Blissus leucopterus, Brachycorynella asparagi, Brevennia rehi, Brevicoryne brassicae, Calocoris norvegicus, Ceroplastes rubens, Ci- mex hemipterus, Cimex lectularius, Dagbertus fasciatus, Dichelapisis- Dyselaphis furis, cus suturellus, Edessa meditabunda, Eriosoma lanigerum, Eurygaster maura, Euschistus heros, Euschistus servus, Helopeltis antonii, Helo- peltis teivora, Icerya purchasi, Idioscopus nitidulus, Laodelphax striatel- lus, Leptocorisa, leptocorisa oror- , Macrosiphum euphorbiae, Macrosiphum grana- rium, Macrosiphum rosae, Macro steles quadrilineatus, Mahanarva frimbiolata, Metopolophium dirhodum, Mictis longicornis, Myzus persise, Nephotettix cinctipes, Neurocolpus longirostris, Nezara viridula, Nilaparvata lugens, Parlatoria pergandii, Parlatoria zizipi, Peregrinyyococis, Phylocera phidisis, Phylocera, Phidisis, relativus, Piezodorus guildinii lineatus Poecilocapsus, Psalus vaccinicola, Pseudacista perseae, brevipes Pseudococcus, Quadraspidiotus perniciosus, Rhopalosiphum maidis, Rhopalosiphum padi, oleae Saissetia, castanea Scaptocoris, Schizaphis graminum, avenae Sitobion, Sogatella furcifera, Trialeurodes vaporariorum, Trialeurodes abutiloneus, Unaspis yanonensis, and Zulia entrerriana.
[00313] In another embodiment, Formula One molecules can be used to control pests of the Order Hymenoptera. A non-exhaustive list of particular genera includes, but is not limited to, Acromyrmex spp., Atta spp., Camponotus spp., Diprion spp., Formicaspp., Monomorium spp., Neodiprionspp., Pogonomyr-mex spp., Polistes spp. , Solenopsis spp., Vespula spp., And Xylocopa spp. A non-exhaustive list of particular species includes, but is not limited to, Atalia rosae, Atta texana, Iridomyrmex humilis, Monomorium minimum, Monomorium pharaonis, Solenopsis invicta, Solenopsis geminata, Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni, and Tapinoma sessile.
[00314] In another embodiment, the Formula One molecules can be used to control pests of the Isoptera Order. A non-exhaustive list of particular genera includes, but is not limited to, Coptotermes spp., Cornitermes spp., Criptotermes spp., Heterotherms spp., Kalotermesspp., Incisitermes spp., Macrotermes spp., Marin Ginitermes spp., Microcerotermes spp., Procornitermes spp., Reticulimeres spp., Schedorhinotermes spp., And Zootermopsis spp. A non-exhaustive list of particular species includes, but is not limited to, Coptotermes curvignathus, Coptotermes frenchi, Coptotermes formo-sanus, Heterotermes aureus, Microtermes obesi, Reticulitermes banyu- lensis, Reticulitermes grassei, Reticulitermes flavipes, Reticulitermes hgeni, Reticulitermes hgeni, Reticulitermes hgeni, Reticulitermes hgeni, Reticulitermes hgeni, Reticulitermes hgeni, Reticulitermes santonensis, Reticulitermes speratus, Reticulitermes tibialis, and Reticulitermes virginicus.
[00315] In another embodiment, the Formula One molecules can be used to control pests of the Order Lepidoptera. A non-exhaustive list of particular genera includes, but is not limited to, Adoxophyes spp., Agrotis spp., Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilospp., Chrysodeixis spp., Colias spp., Crambus spp. ., Diaphania spp., Diatraea spp., Earias spp., Ephestia spp., Epimecis spp., Feltia spp., Gortyna spp., Helicoverpa spp., Heliotis spp., Indarbela spp., Litocolletis spp., Loxagrotis spp., Malacosoma spp., Peridroma spp., Phyllonorycter spp., Pseudaletia spp., Sesamia spp., Spodoptera spp., Synantedon spp., And Yponomeuta spp. A non-exhaustive list of particular species includes, but is not limited to, Achaea janata, Adoxophyes orana, Agrotis ipsilon, Alabama argillacea, Amorbia cuneana, Amyelois transitella, Anacamptodes defectaria, Anarsia lineatella, Anomis sabulifera, Anticarsia gemmatalis, Archips argyrospana , Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes, Borbo cinnara, Bucculatrix thurberiella, Capua reticulana, Carposina niponensis, Chlumetia transversa, Choristoneura rosaceana, Cnaphalocrocis medinalis, Copusia, Cossusia, Cossusia, Cossusia, Cossusia pomonella, Darna diducta, Diatraea saccharalis, Diatraea grandiosella, Earias insulana, Earias vittella, Ecdytolopha auran- tianum, Elasmopalpus lignosellus, Ephestia cautella, Ephestia elutella, Ephestia kuehniella, Epinotia aporema, Epiphysiae apema, Epiphysiae eota, Epiphynae, eota eota, eota , Grapholita molesta, Hedylepta indicata, Heli coverpa armigera, Helicoverpa zea, Heliotis vires-cens, Hellula undalis, Keiferia lycopersicella, Leucinodes orbonalis, Leucoptera coffeella, Leucoptera malifoliella, Lobesia botrana, Loxagrotis albicosta, Lymantria dispar, Lyonetia clerkella, Mahasena coruletti, Mahasena corbetti, Mytimna unipuncta, Neoleucinodes elegantalis, Nymphula depunctalis, Opera rophtera brumata, Ostrinia nubilalis, Oxid / vesulia, Pandemis cerasana, Pandemis heparana, Papilio demodocus, Pectinophora gossypiella, Peridroma saucia, operucorea , Plathypena scabra, Plodia interpunc- tella, Plutella xylostella, Polychrosis viteana, Prays endocarpa, Prays oleae, Pseudaletia unipuncta, Pseudoplusia includens, Rachiplusia nu, Scirpophaga incertulas, Sesamia inferens, Sesamia nonagrioi- Spodoptera exigua, Spodoptera frugiperda, Spodoptera eridani a, Tecla basilides, Tineola bisselliella, Trichoplusia ni, Tuta absoluta, Zeuzera coffeae, and Zeuzera pirina.
[00316] In another embodiment, Formula One molecules can be used to control pests of the Malophaga Order. A non-exhaustive list of particular genera includes, but is not limited to, Anaticola spp., Bovicola spp., Chelopistes spp., Goniodes spp., Mannacanthus spp., And Trichodectesspp. A non-exhaustive list of particular species includes, but is not limited to, Bovicola bovis, Bovicola caprae, Bovicola ovis, Chelopistes meleagridis, Goniodes dissimilis, Goniodes gigas, Menacanthus stramineus, Menopon gaWnae, and Trichodectes canis.
[00317] In another embodiment, the Formula One molecules can be used to control pests of the Order Ortoptera. A non-exhaustive list of particular genera includes, but is not limited to, Melanoplus spp., And Pterophylla spp. A non-exhaustive list of particular species includes, but is not limited to, Anabrus simplex, African Gryllotalpa, Gryllotalpa australis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla, Locusta migradora, Microcentrum retinerve, Schistocerca gregaria, and Scudderia furcata.
[00318] In another embodiment, the Formula One molecules can be used to control pests of the Order Siphonaptera. A non-exhaustive list of particular species includes, but is not limited to, Ceratophyllus gaWnae, Ceratophyllus niger, Ctenocephalides canis, Ctenocephalides felis, and Pulex irritans.
[00319] In another embodiment, Formula One molecules can be used to control pests of the Order Thysanoptera. A non-exhaustive list of particular genera includes, but is not limited to, Caliothrips spp., Frankliniella spp., Scirtothripsspp., And Thrips spp. A non-exhaustive list of sp. particular sp. includes, but is not limited to, Frankliniella fusca, Frankliniella occidentalis, Frankliniella schultzei, Frankliniella williamsi, Heliothrips haemorrhoidalis, Rhipiphorothrips cruentatus, Scirtothrips citri, Scirtothrips dorsalis, and Taeniothrips rhopalantenni, Thrips, Thrips, Thrips, Thrips, Thrips, Thrips, Thrips, Thrips
[00320] In another embodiment, Formula One molecules can be used to control pests of the Order Thysanura. A non-exhaustive list of particular genera includes, but is not limited to, Lepisma spp. and Termobia spp.
[00321] In another embodiment, Formula One molecules can be used to control pests of the Order Acarina. A non-exhaustive list of particular genera includes, but is not limited to, Acarus spp., Aculopsspp., Boophilus spp., Demodex spp., Dermacentor spp., Epitrimerus spp., Eriophyesspp., Ixodesspp., Oligonychus spp., Panonychus spp., Rhizogliphus spp., And Tetranychus spp. A non-exhaustive list of particular species includes, but is not limited to, Acarapis woodi, Acarus siro, Aceria mangiferae, Aculops lyco-persici, Aculus pelekassi, Aculus schlechtendali, Amblyomma america-num, Brevipalpus obovatus, Brevipalpus phoenicis, Dermacentor vari- , Dermatophagoides pteronyssinus, Eotetranychus carpini, Noto-edres cati, Oligonychus coffeae, Oligonychus ilicis, Panonychus citri, Panonychus ui mi, Phyllocoptruta oleivora, Polyphagotarsonemus latus, Rhipicephalus rainee, Tyrant, scorpion and var.
[00322] In another embodiment, Formula One molecules can be used to control plague of the Symphyla Order. A non-exhaustive list of sp. particular includes, but is not limited to, Scutigerella immaculata.
[00323] In another embodiment, Formula One molecules can be used to control pests of Phylum Nematoda. A non-exhaustive list of particular genera includes, but is not limited to, Aphelenchoides spp., Belonolaimus spp., Criconemella spp., Ditilen- chus spp., Heterodera spp., Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp., and Radopholus spp. A non-exhaustive list of particular sp. it includes, but is not limited to, Dirofilaria immitis, Heterodera zeae, Meloidogyne incognita, Meloidogyne jacavica, Onchocerca volvulus, Radopholus similis, and Rotylenchulus renifis.
[00324] For additional information see “Handbook of Pest Control - Te Behavior, Life History, and Control of Household Pests” by Arnold Malis, 9th Edition, copiright 2004 by GIE Media Inc. APPLICATIONS
[00325] Formula One molecules are generally used in amounts of about 0.01 grams per hectare to about 5000 grams per hectare to provide control. Quantities of about 0.1 grams per hectare to about 500 grams per hectare are generally preferred, and quantities of about 1 gram per hectare to about 50 grams per hectare are generally more preferred.
[00326] The area to which the Formula One molecule is applied can be any uninhabited area (or can be uninhabited, or crossed by) a plague, for example: where crops, trees, fruits, cereals, forage species, grapevines, grass and ornamental plants, are developed; where domesticated animals are residing; the interior or exterior of building surfaces (such as places where grain is stored), the building materials used in construction (such as impregnated wood), and the soil around the buildings. Particular harvest areas for employing a Formula One molecule include areas where apples, corn, sunflowers, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes , peppers, crucifers, pears, tobacco, almonds, sugar beets, beans and other valuable crops are developed or seeds are being planted. It is also advantageous to employ ammonium sulfate with a Formula One molecule when growing several plants.
[00327] Pest control generally means that pest populations, pest activity, or both, are reduced in one area. This can happen when: plague populations are repulsed from an area; when pests are disabled in or around the area; or pests are exterminated, in whole or in part, in or around the area. Of course, a combination of these results can occur. Generally, plague populations, activity, or both are desirably reduced by more than fifty percent, preferably more than 90 percent. Generally, the area is not on or about a human; consequently, the site is generally a non-human area.
[00328] Formula One molecules can be used in mixtures, applied simultaneously or sequentially, alone or with other compounds to enhance the vigor of the plant (for example, to develop a better root system, to better withstand stressful growing conditions ). Such other compounds are, for example, compounds that modulate the plant's ethylene receptors, most notably 1-methylcyclopropene (also known as 1-MCP). In addition, such molecules can be used during times when pest activity is low, just as before plants that are beginning to grow to produce valuable agricultural commodities. Such moments include the start of the planting season when the pressure of the plague is usually low.
[00329] Formula One molecules can be applied to the fruiting and leaf portions of plants to control pests. The molecules will be in direct contact with the plague, or the plague will consume the pesticide when eating leaf, fruit paste, or extract the sap, which contains the pesticide. Formula One molecules can also be applied to the soil, and when applied in this way, pests eating root and stem can be controlled. The roots can absorb a molecule by taking it into the leaf portions of the plant to control pests by eating the sap and chewing the soil above.
[00330] Generally, with baits, the baits are placed on the ground where, for example, termites can come in contact with, and / or be attracted to the bait. Baits can also be applied to a building surface, (horizontal, vertical, or sloping surface) where, for example, ants, termites, cockroaches and flies, can come in contact with, and / or be attracted to, the bait. The baits can comprise a Formula One molecule.
[00331] Formula One molecules can be encapsulated inside, or placed on the surface of a capsule. The size of the capsules can vary from the nanometer size (about 100-900 nanometers in diameter) to the micrometer size (about 10-900 microns in diameter).
[00332] Because of the unique ability of some pests' eggs to resist certain pesticides, repeated applications of Formula One molecules may be desirable to control newly emerged larvae.
[00333] The systemic movement of pesticides in plants can be used to control pests in a portion of the plant by applying (for example spraying an area) the Formula One molecules to a different portion of the plant. For example, the control of foliar feeding insects can be achieved by irrigation by gutting or application by furrow, treating the soil with, for example, soaking the soil pre- or post-planting, or treating the seeds of a plant before planting. Seed treatment can be applied to all types of seeds, including those from which plants genetically modified to express specialized characteristics will germinate. Representative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis or other insecticidal toxins, those expressing herbicidal resistance, such as “Roundup Ready” seed, or those with “stacked” genes expressing insecticidal toxins, herbicidal resistance, enhancement nutrition, drought resistance, or any other beneficial characteristics. In addition, such seed treatments with Formula One molecules can also enhance a plant's ability to improve resistance to stressful growing conditions. This results in a more vigorous, healthier plant, which can induce higher yields at harvest time. Generally, about 1 gram of Formula One molecules at about 500 grams per 100,000 seeds is expected to provide good benefits, amounts of about 10 grams to about 100 grams per 100,000 seeds are expected to provide better benefits, and amounts of about 25 grams to about 75 grams per 100,000 semesters is expected to provide even better benefits.
[00334] It should be readily apparent that Formula One molecules can be used on, in, or around genetically modified plants to express specialized characteristics, such as Bacillus thuringiensis or other insecticidal toxins, or those expressing herbicidal resistance, or those with "stacked" foreign genes expressing insecticidal toxins, herbicidal resistance, nutrition enhancement, or any other beneficial characteristics.
[00335] The Formula One molecules can be used to control endoparasites and ectoparasites in the sector of veterinary medicine or in the field of preparation of non-human animals. The Formula One molecules are applied, such as by oral administration in the form of, for example, tablets, capsules, drinks, granules, by dermal application in the form of, for example, dipping, spraying, pouring, staining, and dusting, and by parenteral administration in the form of, for example, an injection.
[00336] Formula One molecules can also be advantageously employed in the maintenance of livestock, for example, cattle, sheep, pigs, chickens, and goose. They can also be used advantageously on pets such as horses, dogs, and cats. The particular pets to control would be fleas and ticks that are annoying to such animals. Suitable formulations are administered orally to the animals by drinking water or food. The dosages and formulations that are suitable depend on the species.
[00337] Formula One molecules can also be used to control parasitic worms, especially from the intestine, in the animals listed above.
[00338] Formula One molecules can also be used in therapeutic methods for the care of human health. Such methods include, but are limited to, oral administration in the form of, for example, tablets, capsules, drinks, granules, and by dermal application.
[00339] Pests around the world have been migrating to new environments (for such a plague) and, therefore, turning a new invasive species into such a new environment. Formula One molecules can also be used in such new invasive species to control them in such a new environment.
[00340] Formula One molecules can also be used in an area where plants, such as crops, are developed (for example, pre-planting, planting, pre-harvest) and where there are low levels (even without presence of pests that can commercially harm such plants. The use of such molecules in such an area is to benefit the plants being developed in the area. Such benefits may include, but are not limited to, improving the health of a plant, improving the production of a plant (for example, increased biomass and / or increased content of valuable ingredients), improving the vigor of a plant (for example , improved plant growth and / or greener leaves), improving the quality of a plant (for example, improved content or composition of certain ingredients), and improving the plant's abiotic and / or biotic stress tolerance.
[00341] Before a pesticide can be used or sold commercially, that pesticide undergoes lengthy evaluation processes by various government authorities (local, regional, state, national, and international). Bulky data requirements are specified by regulatory authorities and should be controlled by submitting and generating data by the product registrant or by a third meeting on behalf of the product registrants, often using a computer with a connection to the World Wide Web These government officials then review such data and if a security determination is completed, provide the potential user or vendor with product registration approval. Therefore, in that location where product registration is granted and supported, such a user or seller may employ or sell that pesticide.
[00342] The molecule according to Formula One can be tested to determine its effectiveness against pests. In addition, the method of action studies can be conducted to determine whether that molecule has a different method of action than other pesticides. Therefore, such acquired data can be disseminated, such as over the internet, to third parties. The headings in this document are for convenience only and should not be used to interpret any part in this regard. TABLE SECTION


Table ABC: Biological results




* Tested at 12.5 gg / cm2 * Tested at 0.5 gg / cm2

权利要求:
Claims (2)
[0001]
1. Composition, characterized by the fact that it comprises a molecule selected from one of the following:
[0002]
2. Process, characterized by the fact that it comprises applying a composition, as defined in claim 1, to a location to control a pest, in an amount sufficient to control such a pest.

类似技术:

---

公开号 | 公开日 | 专利标题

---

US9440964B2|2016-09-13|Pesticidal compositions and processes related thereto

---

RU2605537C2|2016-12-20|Pesticide compositions and methods relating thereto

---

KR102194088B1|2020-12-22|Molecules having certain pesticidal utilities, and intermediates, compositions, and processes related thereto

---

JP5965910B2|2016-08-10|Pesticide compositions and methods related thereto

---

JP5894607B2|2016-03-30|Pesticide compositions and related methods

---

MX2014005086A|2014-08-22|Pesticidal compositions and processes related thereto.

---

JP6054307B2|2016-12-27|Pesticide compositions and related methods

---

BR122014017503A2|2018-08-14|PESTICIDATED COMPOSITIONS AND PROCESSES RELATED TO THEM

---

US20150196033A1|2015-07-16|Pesticidal compositions and processes related thereto

---

ES2856845T3|2021-09-28|Molecules that have certain pesticide utilities, and intermediates, compositions and processes related to them

---

MX2014009346A|2014-09-01|Pesticidal compositions and processes related thereto.

---

BR112017000411B1|2020-05-12|MOLECULES AND PESTICIDE COMPOSITIONS

---

ES2744559T3|2020-02-25|Triazole derivatives having pesticide utility, and related intermediates, compositions and procedures

---

ES2759020T3|2020-05-07|Molecules having certain pesticide utilities, and intermediates, compositions, and processes related thereto

---

BR112017000512B1|2021-10-26|MOLECULES, PESTICIDE COMPOSITIONS, AND NON-THERAPEUTIC PROCESS

---

NZ619869B2|2015-06-30|Pesticidal compositions and processes related thereto

同族专利:

---

公开号 | 公开日

---

AU2012282693B2|2015-11-05|

---

CN103826452A|2014-05-28|

---

RU2596946C2|2016-09-10|

---

KR20140045542A|2014-04-16|

---

CA2841450C|2019-04-23|

---

CA2841450A1|2013-01-17|

---

AP2014007364A0|2014-01-31|

---

NZ619869A|2015-03-27|

---

ZA201401045B|2016-07-27|

---

MA35341B1|2014-08-01|

---

BR112014000688A2|2017-06-13|

---

JP2014520851A|2014-08-25|

---

CO6870049A2|2014-02-20|

---

AU2012282693A1|2014-01-30|

---

ES2729947T3|2019-11-07|

---

EP2731430B1|2019-04-03|

---

TWI561511B|2016-12-11|

---

CL2014000098A1|2014-07-11|

---

CN103826452B|2017-02-01|

---

TW201311642A|2013-03-16|

---

US9440964B2|2016-09-13|

---

JP5977348B2|2016-08-24|

---

MX371345B|2020-01-27|

---

WO2013009791A1|2013-01-17|

---

MX2014000468A|2014-06-05|

---

UA115126C2|2017-09-25|

---

EP2731430A1|2014-05-21|

---

EP2731430A4|2015-04-01|

---

US20130019348A1|2013-01-17|

---

AR087119A1|2014-02-12|

---

AP3788A|2016-08-31|

---

US20150197514A1|2015-07-16|

---

RU2014104807A|2015-08-20|

引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

IL38408D0|1970-12-21|1972-04-27|Ciba Geigy Ag|Pesticidal,bactericidal,herbicidal and plant growth controlling compositions containing semicarbzide or dithiobiuret compounds and methods of destroying pests and of controlling the growth of plants by means of such compositions|

---

US4017529A|1972-07-03|1977-04-12|E. I. Du Pont De Nemours And Company|Herbicidal allophanimidates|

---

DE2253027A1|1972-10-28|1974-05-09|Bayer Ag|FUNGICIDALS|

---

US4867780A|1988-07-01|1989-09-19|Ici Americas, Inc.|2-thiazolidine herbicides|

---

ES2095657T3|1992-07-24|1997-02-16|Kumiai Chemical Industry Co|DERIVED FROM TRIAZOL, PROCEDURE FOR OBTAINING THE SAME, A PEST CONTROL AGENT AND PEST CONTROL METHOD.|

---

AU730027B2|1997-04-24|2001-02-22|Dow Agrosciences Llc|Pesticidal 3--5--1,2,4-triazoles|

---

GB9810354D0|1998-05-14|1998-07-15|Pfizer Ltd|Heterocycles|

---

US6413992B1|1998-10-23|2002-07-02|Dow Agrosciences Llc|3--1,2,4-triazole compounds|

---

US6136335A|1998-12-31|2000-10-24|Hughes Institute|Phenethyl-5-bromopyridylthiourea and dihydroalkoxybenzyloxopyrimidine derivatives exhibiting spermicidal activity|

---

RU2259370C2|1999-11-18|2005-08-27|Новартис Аг|Aminoheterocyclamide derivatives eliciting pesticide activity|

---

US6417187B2|2000-04-14|2002-07-09|Dow Agrosciences Llc|1,2,4-triazole based compounds that can be used as insecticides or acaricides and processes|

---

US20030008791A1|2001-06-06|2003-01-09|Lonza Inc.|Non-alcoholic hand sanitizer|

---

WO2003051315A2|2001-12-18|2003-06-26|Merck & Co., Inc.|Heteroaryl substituted triazole modulators of metabotropic glutamate receptor-5|

---

KR20050111306A|2002-11-19|2005-11-24|아칠리온 파르마세우티칼스 인코포레이티드|Substituted aryl thioureas and related compounds; inhibitors of viral replication|

---

DE10326386A1|2003-06-12|2004-12-30|Bayer Cropscience Ag|N-heterocyclyl-phenyl-substituted cyclic ketoenols|

---

CA2539042A1|2003-09-24|2005-04-07|Merck Sharp & Dohme Limited|Gamma-secretase inhibitors|

---

EA014881B1|2004-03-05|2011-02-28|Ниссан Кемикал Индастриз, Лтд.|Substitited alkylbenzene derivatives|

---

TWI402034B|2005-07-28|2013-07-21|Dow Agrosciences Llc|Agricultural compositions comprising an oil-in-water emulsion based on oily globules coated with a lamellar liquid crystal coating|

---

KR20080106176A|2006-01-10|2008-12-04|이노베이폼 테크놀로지스 엘엘씨|Pesticide delivery system|

---

CN101400662B|2006-03-10|2012-11-14|日产化学工业株式会社|Substituted isoxazoline compound and pest control agent|

---

US20080045491A1|2006-08-15|2008-02-21|Fitchmun Mark I|Surface sanitizer|

---

US20080262057A1|2007-04-20|2008-10-23|Dow Agrosciences Llc|Diarylisoxazolines|

---

WO2009032861A1|2007-09-04|2009-03-12|The Scripps Research Institute|Substituted pyrimidinyl-amines as protein kinase inhibitors|

---

ES2601518T3|2008-02-12|2017-02-15|Dow Agrosciences Llc|Pesticide Compositions|

---

DK2396339T3|2009-02-11|2014-10-13|Dow Agrosciences Llc|pesticide Compositions|

---

AU2010279377B2|2009-08-07|2014-07-03|Dow Agrosciences Llc|Pesticidal compositions|

---

DK2461687T3|2009-08-07|2015-12-21|Dow Agrosciences Llc|Pesticidal compositions|

---

AR082638A1|2010-08-26|2012-12-19|Dow Agrosciences Llc|DERIVATIVES OF TETRAHYDROPIRY USEFUL AS PESTICIDES|

---

DK2672819T3|2011-02-07|2018-02-26|Dow Agrosciences Llc|PESTICIDE COMPOSITIONS AND PROCEDURES RELATED TO IT|

---

JP6054307B2|2011-02-09|2016-12-27|ダウ アグロサイエンシィズ エルエルシー|Pesticide compositions and related methods|

---

BR112014033104A2|2012-07-09|2017-06-27|Dow Agrosciences Llc|pesticide compositions and processes related thereto|ES2601518T3|2008-02-12|2017-02-15|Dow Agrosciences Llc|Pesticide Compositions|

---

AU2010279377B2|2009-08-07|2014-07-03|Dow Agrosciences Llc|Pesticidal compositions|

---

CA3085086A1|2011-12-06|2013-06-13|Delta Faucet Company|Ozone distribution in a faucet|

---

US8916183B2|2012-02-02|2014-12-23|Dow Agrosciences, Llc.|Pesticidal compositions and processes related thereto|

---

IN2014DN09428A|2012-04-18|2015-07-17|Dow Agrosciences Llc|

---

US20140275564A1|2013-03-13|2014-09-18|Dow Agrosciences Llc|Process for the preparation of certain triaryl rhamnose carbamates|

---

WO2014158648A1|2013-03-13|2014-10-02|Dow Agrosciences Llc|Preparation of 1,3--1,2,4-triazoles|

---

WO2014186027A1|2013-03-13|2014-11-20|Dow Agrosciences Llc|Process for the preparation of triaryl rhamnose carbamates|

---

US9376401B2|2013-03-13|2016-06-28|Dow Agrosciences Llc|Preparation of 1,3--1,2,4-triazoles and intermediates therefrom|

---

WO2014158650A1|2013-03-13|2014-10-02|Dow Agrosciences Llc|Preparation of triaryl rhamnose carbamates|

---

WO2014158644A1|2013-03-13|2014-10-02|Dow Agrosciences Llc|Process for the preparation of triaryl rhamnose carbamates|

---

US20140275560A1|2013-03-13|2014-09-18|Dow Agrosciences Llc|Preparation of 1,3--1,2,4-triazoles and intermediates therefrom|

---

WO2014163933A1|2013-03-13|2014-10-09|Dow Agrosciences Llc|Process for preparation of triaryl pesticide intermediate|

---

US20140275504A1|2013-03-13|2014-09-18|Dow Agrosciences Llc|Process for the preparation of certain triaryl rhamnose carbamates|

---

US10246452B2|2013-03-14|2019-04-02|Dow Agrosciences Llc|Molecules having certain pesticidal utilities, and intermediates, compositions, and processes related thereto|

---

BR122016021771B1|2013-03-14|2021-04-27|Dow Agrosciences Llc|PROCESSES TO PRODUCE MOLECULES PRESENTING CERTAIN PESTICIDED UTILITIES|

---

TW201534217A|2013-07-11|2015-09-16|Agrofresh Inc|Methods and compositions of granule formulations|

---

PL3022185T3|2013-07-15|2018-02-28|Basf Se|Pesticide compounds|

---

CN105636445B|2013-10-17|2018-12-07|美国陶氏益农公司|The method for preparing Pesticidal compound|

---

CN105636441B|2013-10-17|2018-06-15|美国陶氏益农公司|The method for preparing Pesticidal compound|

---

CA2925952A1|2013-10-17|2015-04-23|Dow Agrosciences Llc|Processes for the preparation of pesticidal compounds|

---

CN105636443A|2013-10-17|2016-06-01|美国陶氏益农公司|Processes for the preparation of pesticidal compounds|

---

US9078443B1|2014-01-31|2015-07-14|Fmc Corporation|Methods for controlling weeds using formulations containing fluthiacet-methyl and HPPD herbicides|

---

RU2564893C1|2014-05-20|2015-10-10|Александр Александрович Кролевец|Method of producing nanocapsules of gibberellic acid|

---

RU2564892C1|2014-05-20|2015-10-10|Александр Александрович Кролевец|Method of producing nanocapsules of 2-cis-4-trans-abscisic acid|

---

CN103975935B|2014-05-28|2016-08-24|陕西上格之路生物科学有限公司|A kind of bactericidal composition preventing and treating crops soil-borne disease|

---

TW201603707A|2014-06-24|2016-02-01|陶氏農業科學公司|Molecules having certain pesticidal utilities, and intermediates, compositions, and processes related thereto|

---

TW201625564A|2014-07-23|2016-07-16|陶氏農業科學公司|Molecules having certain pesticidal utilities, intermediates, compositions, and processes, related thereto|

---

TW201625563A|2014-07-28|2016-07-16|陶氏農業科學公司|Molecules having certain pesticidal utilities, and intermediates, compositions, and processes related thereto|

---

TWI670012B|2014-07-28|2019-09-01|美商陶氏農業科學公司|Molecules having certain pesticidal utilities, and intermediates, compositions, and processes related thereto|

---

US9029555B1|2014-07-31|2015-05-12|Dow Agrosciences Llc|Process for the preparation of 3-pyridine|

---

CN107074774A|2014-08-19|2017-08-18|美国陶氏益农公司|The method for preparing 3pyridines|

---

TWI677491B|2014-08-26|2019-11-21|美商陶氏農業科學公司|Molecules having certain pesticidal utilities, and intermediates, compositions, and processes related thereto|

---

CN107074775A|2014-09-12|2017-08-18|美国陶氏益农公司|The preparation method of 3pyridines|

---

WO2016099929A1|2014-12-15|2016-06-23|Dow Agrosciences Llc|Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto|

---

CN104521982B|2014-12-23|2018-04-27|广东中迅农科股份有限公司|Containing fluorine ketone sulphur grass An He the Herbicidal combinations of metamifop|

---

CN104909885A|2015-05-29|2015-09-16|河南科技学院|Compound pesticide-fertilizer composition capable of controlling powdery mildew of Cedrela sinensis, and production method and application thereof|

---

CN108135174B|2015-09-04|2021-05-04|美国陶氏益农公司|Molecules having pesticidal utility, and intermediates, compositions and methods related thereto|

---

WO2017040742A1|2015-09-04|2017-03-09|Dow Agrosciences Llc|Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto|

---

US9617253B2|2015-09-04|2017-04-11|Dow Agrosciences Llc|Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto|

---

WO2017040194A1|2015-09-04|2017-03-09|Dow Agrosciences Llc|Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto|

---

CN105475295A|2015-12-17|2016-04-13|北京燕化永乐生物科技股份有限公司|Weeding composition|

---

MX2018007527A|2015-12-22|2018-09-07|Syngenta Participations Ag|Pesticidally active pyrazole derivatives.|

---

AU2017211678B2|2016-01-25|2019-05-02|Corteva Agriscience Llc|Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto|

---

AU2017212303B2|2016-01-25|2019-09-12|Corteva Agriscience Llc|Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto|

---

CN106226416B|2016-07-12|2018-12-04|中华人民共和国徐州出入境检验检疫局|The detection method of sulfoxaflor residual quantity in garlic|

---

CN106632270B|2016-09-27|2021-05-25|贵州省茶叶研究所|Glutamic acid-bromopyrrole nitrile coupling compound and preparation method thereof|

---

CN109906033A|2016-11-09|2019-06-18|美国陶氏益农公司|Molecule and relative intermediate, composition and method with certain desinsection effectiveness|

---

CA3045224A1|2016-12-16|2018-06-21|Basf Se|Pesticidal compounds|

---

BR112019005145A2|2016-12-21|2019-06-04|Dow Agrosciences Llc|molecules having certain pesticidal uses, and intermediates, compositions and processes related thereto|

---

US10233155B2|2016-12-29|2019-03-19|Dow Agrosciences Llc|Processes for the preparation of pesticide compounds|

---

WO2018125818A1|2016-12-29|2018-07-05|Dow Agrosciences Llc|Processes for the preparation of pesticidal compounds|

---

WO2018125815A1|2016-12-29|2018-07-05|Dow Agrosciences Llc|Processes for the preparation of pesticidal compounds|

---

AU2018241406B2|2017-03-28|2021-11-11|Basf Se|Pesticidal compounds|

---

TW201837016A|2017-03-31|2018-10-16|美商陶氏農業科學公司|Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto|

---

EP3728199A1|2017-12-21|2020-10-28|Basf Se|Pesticidal compounds|

---

EP3643705A1|2018-10-24|2020-04-29|Basf Se|Pesticidal compounds|

---

WO2020109039A1|2018-11-28|2020-06-04|Basf Se|Pesticidal compounds|

---

WO2020113094A1|2018-11-30|2020-06-04|Nuvation Bio Inc.|Pyrrole and pyrazole compounds and methods of use thereof|

---

WO2020229398A1|2019-05-14|2020-11-19|Bayer Aktiengesellschaft|-substituted pyrazoles and triazoles as pest control agents|

---

EP3766879A1|2019-07-19|2021-01-20|Basf Se|Pesticidal pyrazole derivatives|

---

WO2021219513A1|2020-04-28|2021-11-04|Basf Se|Pesticidal compounds|

---

KR20220019151A|2020-08-06|2022-02-16|안동대학교 산학협력단|Composition for inhibiting mosquitoes comprising aspirin and method for controlling mosquitoes using it|

法律状态:
2019-07-30| B06U| Preliminary requirement: requests with searches performed by other patent offices: suspension of the patent application procedure|

---

2019-12-10| B06F| Objections, documents and/or translations needed after an examination request according art. 34 industrial property law|

---

2020-03-10| B07A| Technical examination (opinion): publication of technical examination (opinion)|

---

2020-05-19| B07A| Technical examination (opinion): publication of technical examination (opinion)|

---

2020-06-16| B09A| Decision: intention to grant|

---

2020-08-18| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 11/07/2012, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

---

申请号 | 申请日 | 专利标题

---

US201161506743P| true| 2011-07-12|2011-07-12|

---

US61/506,743|2011-07-12|

---

PCT/US2012/046131|WO2013009791A1|2011-07-12|2012-07-11|Pesticidal compositions and processes related thereto|

---