• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    This invention relates to heterocyclic compounds, in particular the preparation of 1H, 3H-pyrrolo (1,2-C) thiazole in the form of racemates or enantiomers general-ly f where R @ 1 -H, halogen, dialkylamino or alkoxy X- O, S, CH 2 , NH, C (O), carbonylvinylene AR is naphthyl, pyridyl, thienyl, phenyl, halophenyl, C 1 -C 4 -alkoxyphenyl, di-C 1 -C 4 -alkylaminophenyl, which have a inhibitory effect on PAF-ACETHER. The goal is to create new active and low toxic substances of the specified class. The synthesis is carried out by the reaction of the corresponding amine with racemic or optically acid chloride with the subsequent isolation of the target product. New substances have low toxicity (LD 50 = 300-900 mg / kg), are active at inhibitory concentrations of 1-1000 nmol, and are fixed on platelet receptors at much lower doses than the known analogue.
    公开号:SU1528323A3
    申请号:SU874202952
    申请日:1987-07-02
    公开日:1989-12-07
    发明作者:Фабр Жан-Луи；Жам Клод；Лаве Даниель
    申请人:Рон-Пуленк Санте (Фирма)；
    IPC主号:
    专利说明:

    2X s3Q-C (0) -NH
    X-AG
    The invention relates to the field of obtaining new derivatives of 1H, ZN-pyrrolo (1,2-e) thiazole of the general formula
    CONH- X-Ar
    Nr pi
    where R is hydrogen, halogen, dialkylamino, or alkoxy; X is oxygen or sulfur, imino, carbonyl, carbonylvinylene or methylene;
    Ar is naphthyl, pyridyl, thienyl or phenyl, unsubstituted or substituted by halogen, apkyl, alkoxy or dialkylamino, in which the alkyl parts contain,
    in the form of racemates or enantiomers, which have a certain inhibitory effect on PAF-acether.
    The purpose of the invention is the development based on the known methods of the method to
    00
    00 to
    with

    04
    New derivatives of 1H, ZN-pyrrolo (1,2-c) thiazoles with valuable pharmacological properties with low toxicity.
    Example 1. To a solution of 2.8 g of 3-phenoxyaniline and 3.05 g of triethyl amine in 100 cm of dioxane, heated to a temperature of about 60 ° C, 4.5 g of 7-chlorofor are added for 5 minutes at 60-68 ° C. mil-3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-th) thiazol hydrochloride. The resulting suspension is heated with stirring at a temperature of about 100 ° C for 6 hours and 15 minutes, then stirred at a temperature of about 20 ° C for 16 hours. The solvent is evaporated under reduced pressure (20 mm Hg 2.7 kPa) at a temperature of 60 C. The residue is dissolved in 250 cm3 of methylene chloride. The resulting solution is washed twice with just 200 cm of distilled water, twice with 200 cm of an aqueous solution of 4 N sodium, and twice with 200 cm of distilled water:
    then dried over anhydrous magnesium sulphate, 0.5 g of bleaching charcoal is added, filtered to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 50 ° C. 6.7 g of crude product are obtained. . This product is dissolved in 25 cm of boiling isopropanol. 0.5 g of bleaching charcoal is introduced into the resulting solution and filtered while hot. The filtrate is cooled to a temperature of about 4 ° C for 3 hours. The crystallized crystals are separated by filtration, washed four times with 20 cm of isopropanol, then three times with 75 cm of diethyl ether and dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 20 ° C in the presence of potassium tablets. Thus, 2.1 g of N- (3-phenoxyphenyl) -3- (3-pyridyl) -1H, 3H-pyrrolo (1, 2-e) - 7-thiazolecarboxamide are obtained in the form of cream-colored crystals with m.p. . 144 ° C.
    Example2. To a solution of 16.1 g of 3-aminobenzophenone and 16.5 g of triethyl amine in 420 cm of dioxane, heated to a temperature of about 60 ° C, 24.5 g of acid chloride are added in 5 minutes at 60-72 ° C.
    Read (+) - 3- (3-pyridyl) -1H, 3H-pyrrolo (, 2-c) -7-thiazolecarboxylic acid hydrochloride. The resulting suspension is heated with stirring at a temperature
    about 5 0
    five
    O., Q
    five
    0
    five
    about 6 hours and 30 minutes, then stirred at a temperature of about 20 ° C for 16 hours, the solvent is evaporated under reduced dosing (20 mm Hg: 2.7 kPAh and a temperature of about 60 ° C. the residue is 750 ml of ethyl acetate. The resulting solution is washed three times with 800 cm of distilled water, two times with 600 cm of an aqueous saturated sodium bicarbonate solution and two times with 600 cm of distilled water, then dried on anhydrous magnesium sulfate, 0 g of bleaching charcoal is added, filtered and concentrated to dryness under reduced pressure at a temperature of about 60 ° C. 36 g of crude product are obtained in this way, which is dissolved in 200 cm of a boiling mixture of ethanol and water (85:15 by volume). the resulting solution was injected with 5 g of bleaching charcoal and filtered hot, and the filtrate was cooled to about 20 ° C for 3 hours. The crystals were filtered and washed three times with 75 cm (mixtures of ethanol and water 85:15 volume) and four times 200 cm of diethyl ether, then dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 20 ° C in the presence of potassium tablets. Thus, 20.7 g of (+) - N- (3-benzenephenyl) -3- (3-pyridyl) -1H, ZN-pyrrolo (1,2-e) -7-thiazolecarboxamide are obtained in the form of hydrate in the form of cream crystals. colors with m.p. 109 C.
    , 5 ± 1 ° (, 02; dimethylformamide).
    Example To a suspension of 9 g of 3- (1-naphthoyl) -aniline and 7.35 g of triethylamine in 150 cm of dioxane heated to a temperature of about 40 ° C, 10.95 g are added during 10 minutes at 40-50 ° C. -chloroformyl-3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-e) thiazol hydrochloride. The reaction mixture is heated to a temperature of about 85 ° C for 8 hours, then the solvent is distilled off under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 50 ° C. The residue is diluted with stirring
    ma
    with a mixture of 500 cm of water and 200 cm of ethyl acetate. The organic phase is separated and the aqueous phase is extracted twice with 400 cm of ethyl acetate. The organic phases are combined, washed three times.
    50 ° C
    300 cm of distilled water, dried over anhydrous magnesium sulphate, 0.9 g of decolorizing carbon is added, filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 16.5 g of crude product are obtained which is dissolved in 150 cm of ethyl acetate. To the resulting solution was added 20 g of silica (0.063-0.2 mm), filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 40 ° C. The resulting product was dissolved in 16 see ethyl acetate. The crystals formed are separated by filtration, then diluted with 250 cm of ethyl acetate in the presence of 0.25 g of decolorizing carbon. The resulting suspension is filtered and the resulting solution is stirred at a temperature of about 20 ° C for 16 hours. The crystallized crystals are filtered, washed three times with 15 cm of ethyl acetate and dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature about . 3.1 g of (1-naphtho) -phenyl-3- (3-pyridyl) -1H 3H-pyrrolo (1,2-c) -7-thiazolecarboxamide are obtained in the form of beige crystals with m.p. 166 ° C.
    Example4. To a solution of 6.6 g of 3- (4-chlorophenoxy) -aniline and 6.1 g of triethylamine in 200 cm of dioxane, heated to a temperature of about 60 ° C, is added in 25 minutes at a temperature of about 9 g of 7-chloroformyl-3- ( 3-pyridyl) -1H, 3N-pyrrolo (1,2-c) thiazole hydrochloride. The resulting suspension is heated with stirring at a temperature of about 100 ° C for 5 hours, then stirred at a temperature of about 20 ° C for 16 hours. The solvent is evaporated under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 65 ° s The residue is dissolved in 400 cm of methylene chloride and the resulting solution is washed twice with 200 cm of distilled water, cm
    an aqueous solution of five times 500 cm of dispersed two times 200 1N sodium and tilirovannogo water, then dried over anhydrous magnesium sulfate, add 0.5 g of bleaching coal, filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2 , 7 kPa) at a temperature of about. Thus obtained 13 g of the product
    50 С
    ,
    t, -

    ten
    15
    20
    25
    thirty
    35
    45
    50
    which is chromatographed on a column with a diameter of 3 cm, containing 120 g of two-silica (0.063-0.2 mm). Elute mixtures of methylene chloride and methanol, taking 300 cm fractions. The first five fractions resulting from the elution with pure methylene chloride are removed. The following nine fractions, formed by elution with a mixture of methylene chloride and methanol (99: 1 by volume), are combined and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 50 ° C. Thus 9.4 g of crude product is obtained, which is dissolved in 100 cm of boiling isopropanol. To the resulting solution was added 0.5 g of decolorizing charcoal and filtered while hot. The resulting filtrate is cooled to about 4 ° C for 16 hours. The crystallized crystals are separated by filtration, washed twice with 20 cm of isopropanol, cooled to about 4 ° C, and twice. 40 cm of diethyl ether, then dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 20 ° C in the presence of potassium in tablets. 6.5 g of (4-chlorophenoxy) -phenyl-3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-c) -7-thiazolecarboxamide are thus obtained in the form of cream-colored crystals with m.p. 140 C.
    Example5. To a solution of 6 g of 3- (2-methylphenoxy-Anshtina and 6.1 g of triethylamine in 150 cm of dioxane heated to a temperature of about 60 ° C, 40 are added in 35 minutes at 61-65 ° C. 9 g of 7-chloroformyl-3 - (3-pyridsh1) -1H, 3N-pyrrolo (1,2-e) thiazole hydrochloride The resulting suspension is heated with stirring at a temperature of about 100 ° C for 6 h, then stirred at a temperature of about 20 ° C for 16 The solvent is evaporated under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about. The residue is dissolved in 400 cm of methylene chloride. The resulting solution
    four
    washed twice with 200 cm of distilled water, twice with 200 cm of water
    55
    solution
    500 cm distilled water
    1 n. And five times
    then
    dried over anhydrous magnesium sulphate; add 0.5 g of bleaching coal; filter and concentrate to dryness under reduced pressure

    (20 mm Hg 2; 7 kPa) at a temperature of about 50 ° C. 7 g of crude product is obtained, which is dissolved in 100 seconds of boiling acetonitrile. Into the resulting solution, 0.5 g of bleaching carbon is introduced and filtered while hot. The filtrate is cooled to 4 ° C for 1 h. The crystals show


    filtered, washed twice with 20 cm of acetonitrile, cooled to a temperature of about 4 ° C, and twice with 20 cm of diethyl ether, then dried under reduced pressure (20 mm RT.St .; 2.7 kPa) at a temperature
    about 20 ° C in the presence of potassium tablets. 3.6 g of (2-methylphenoxy) -phenyl-3- (3-pyridyl) -1H, 3H-pyrrolo (, 2-c) -7-thiazolcarboxamide are thus obtained in the form of white crystals with m.p. . 180 ° C. Example: To a solution of 6 g of 3- (3-methylphenoxy) -aniline and 6, J g of triethylamine in 200 cm of dioxane, heated to a temperature of about 60 ° C, is added in 15 minutes at 60-64 ° C 9 g
    7-chloroformyl 3- (3-pyridyl) -1H, ZN-pyrrolo (1,2-c) thiazol hydrochloride. The resulting suspension is heated with stirring at a temperature of about 100 ° C for 4 h 30 min, then stirred at a temperature of about 20 for 16 h. The solvent is evaporated under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 60 ° C. The resulting residue is dissolved in 350 cm of methylene chloride and the resulting solution is washed twice with 200 cm of distilled water, twice with 200 cm of an aqueous solution of 1N sodium and five times with 500 cm of distilled water, then dried over anhydrous magnesium sulfate, 0, 5 g of decolorizing carbon, filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa at a temperature of about 50 ° C. 13 g of crude product are obtained. This product is dissolved in 50 cm of boiling acetonitrile. B The resulting the solution is injected with 0.5 g of bleaching charcoal and filtered while hot. The filtrate is cooled to about 4 seconds for 2 hours. The crystals are filtered, washed twice with 10 cm of acetonitrile, cooled to 4 ° C, and dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 20 ° C
    eight
    in the presence of potassium tablets. In this way, 6.6 g of product are obtained with a melting point of 148 ° C, which is dissolved in 100 cm of boiling isopropanol. The resulting solution is cooled to 4 ° C for 2 hours. The crystallized crystals are separated by filtration, washed twice with 20 cm.
    isopropanol, cooled to a temperature of about 4 ° C, then twice 40 cm of diesel disulfide ether and dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 20 ° C in the presence of potassium tablets. Thus, 5.5 g of (3-methylphenoxy) -fe- (3-pyridyl) -1H, 3N-pyrrolo (1,2-c) -7-thiazolecarboxamide are obtained in the form of cream-colored crystals with m.p.
    ug c.
    Similarly to these examples, the following compounds were obtained:
    (4-methylphenoxy) -phenyl-3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-с) -7-thiazolecarboxamide in the form of white crystals with m.p. 1 1 o C:
    (2-methoxyphenoxy) -phenyl-3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-c) -7-thiazolecarboxamide in the form of white crystals with mp Pl, 163 C;
    N-GZ- (3-methoxyphenoxy) -phenyl-3- (3-pyridyl), 3N-pyrrolo (1,2-c) -7-thiazole-carboxamide in the form of cream-colored crystals with m.p. 130 ° C;
    (4-methoxyphenoxy) -phenyl 1-3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-с) -7-thiazolecarboxamide in the form of cream-colored crystals with m.p. 120 C;
    N- (2-methoxy-5-phenoxy) -phenyl-3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-c) -7-thiazolecarboxamide in the form of white crystals with m.p. 158 ° C;
    (2-Pyridyloxy) -phenyl-3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-с) -7- | thiazole carboxamide in the form of cream crystals with m. pl. 132 C;
    (3-Pyridyloxy) -phenylJ-3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-c) -7-thiazolecarboxamide in the form of cream crystals with m.p. 154 ° C;
    N- (3-benzoylphenyl) -3- (pyridyl) - 1H, 3N-pyrrolo (1,2-e) -7-thiazolecarboxamide in the form of cream crystals with m.p. 154 ° C;
    (4-Chlorobenzoyl) -phenyl) -3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-с) -7-thiazolecarboxamide in the form of pale yellow crystals with m.p. 176 ° C;
    N-p- (3-methylbenzoyl) -phenyl-3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-с) -7-thiazolecarboxamide in the form of beige crystals with m.p. 164 ° C;
    (4-methoxybenzoyl) -phenyl-3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-с) -7-thiazolecarboxamide in the form of 1sremovy crystals with mp, 140 ° C;
    H- (3-nicotinoyl) -phenyl-3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-с) -7-thiazole-carboxamide in the form of cream crystals with m.p. 160 C;
    N- 3- (2-pyridylcarbonyl) -phenshG - 3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-с) -7-thiazolecarboxamide in the form of cream crystals with m.p.
    (2-Tenoyl) -phenyl-3- (3-pyridyl), 3N-pyrrolo (1,2-c) -7-thiazolecarboxamide in the form of cream crystals with m.p. 172 ° C;
    N- (3-anilinophenyl) -3- (3-pyridyl) - 1H, 3N-pyrrolo (1,2-c) -7-thiazolecarboxamide in the form of white crystals with m.p. 158 С;
    N- (3-benzylphenyl) -3- (3-pyridyl) - 1H, 3N-pyrrolo (1,2-e) -7-thiazolecarboxamide in the form of white crystals with m.p. 139.5 ° C;
    N- (3-phenylthiophenyl) -3- (3-pyridyl) 1H, 3N-pyrrolo (I, 2-c) -7-thiazolecarboxamide in the form of cream crystals with m.p. 152 С;
    N-3- (4-dimethylaminobenzoyl) -3- (3-pyridsh1), ZN-pyrrolo (1,2-с) -7-thiazolecarboxamide in the form of cream crystals with m.p. 208 С;
    .Y- (3-isonicotinoylphenyl) -3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-s) -7-thiazolecarboxamide in the form of white crystals with m.p. 85 ° C;
    (+) - K- (2-chloro-5-benzoylphenyl) -3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-c) -7-thi.azolcarboxamide in the form of cream crystals with m.p. . 1 54 С, fo6j
    -t-48, 5 ± 0.8 ° (, 86; dimethylformamide)
    N-p- (2-methoxybenzoyl) -phenyl-3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-c) -7-thiazolecarboxamide in the form of white crystals with m.p.
    N- (3-cinnamoylphenyl) -3- (3-pyridyl) 1H, 3N-pyrrolo (1, 2-e) -7-thiazolecarboxamide in the form of beige crystals with m.p. 190 ° C;
    N- (5-benzoyl-2-dimethylaminophenyl) -3- (3-pyridyl) -1H, 3N-pyrrolo (1,2-c) -7-thiazolecarboxamide in the form of yellow crystals with m.p. 186 C.
    The resulting compounds have interesting pharmacological properties and, at the same time, have low toxicity. They are found to be active at inhibitory concentrations (C) between 1 and 1000 mmol in the fixation antagonism / o-octadecyl-10-acetyl-2p8-glycerophosphorylcholine-3 (tritiated PAF-acether) test at the sites of platelet receptors for the following method.
    Preparation of washed rabbit platelets.
    Male rabbits weighing approximately 2.5 kg are punctured by the ear artery. Blood is collected in a mixture of citric acid (1.9 mmol), three-sodium citrate (9 mmol), monosodium phosphate (1.75 mmol) and dextrose (5.6 mmol). The blood is centrifuged to 120 g for 20 minutes at 15 ° C. In this way, platelet rich plasma (PPP) is obtained. This plasma is centrifuged to 1000 g for 15 minutes at 15 ° C. The platelet precipitate thus obtained is washed for the first time with Tyrode's solution, modified with 0.35% of short-term bovine albumin (BSA), 2 mmol per liter MgCl2, 0.2 mmol per liter EGTA, then Tyrode solution without EGTA (ethylene glycol bis- (| 3 -amino ethyl ester) -N, N, NN-tetraacetic cyst). Finally, platelets again form a suspension in an experimental buffer solution (buffer A) having the following composition, mmol: NaCl 140; KC l 2.7; , 0.4; MgClj 2; NaHCGj 12; Tris-buffer solution, NS 1 10; dextrose 6.2; BSA (0.25%). The final suspension concentration is adjusted to platelets / cm using this buffer solution.
    Description of the test.
    Buffer solution A, test product, tritiated with PAF-acethes (0.5 mmol, specific activity 80 Ci) and platelets, prepared as described (0.510 platelets), were added successively to a 5 cm tube to obtain a final volume of 3
    mixture for 1
    0.5 cm, and left
    incubation in
    Then add
    Thief A,
    filter the contents of the tube on
    flow
    2
    2 cm of buffer cooled to 4 C, quickly
    h at 20 C rast1
    the WHATMAN / C filter and very quickly rinse the test tube three times with 2 cm of buffer solution A cooled until the filter is dried, placed in a flask containing 4.5 cm of liquid scintillator, and the radioactivity is measured using a universal counter. In this way, the total bound radioactivity is determined. The specific fixation of tritiated PAF-acether was determined by subtracting from the total associated radioactivity the radioactivity remaining on the filter after adding 10 mmol of H- (3-methoxy phenes1) -3- (3-pyryl) -1H, 3H-pyrrolo (1.2 -c) -7-thiazole-carboxamide. For each test product, the test was replicated three times at concentrations increasing
    -to
    ,-four
    FROM IU to 1U mol. For each product, the log probit analysis of the deceleration curve is determined graphically.
    The proposed compounds, in comparison with the known pyrrolothiazols, which have a certain inhibitory effect on PAF-acether, are fixed on platelet receptors at much lower doses, and therefore more suitable for inhibiting the effects of PAF-acether, In addition, they have a small toxicity . Their LD 50 is 300-900 mg / kg for oral administration.

    权利要求:
    Claims (1)
    [1]
    Invention Formula
    The method of obtaining derivatives of 1H, ZN-pyrrolo (1,2-c) thiazole of the general formula
    Iz
    CONH-i VX-Ar
    RI
    where R, is hydrogen, halogen, dialkylamino or alkoxygroup, X is oxygen or sulfur, imino, carbonyl, carbonylvinylene or methylene,
    Ar is naphthyl, pyridyl, thienyl or phenyl, unsubstituted or substituted by halogen, alkyl, alkoxy or dialkylamino, in which the alkyl parts contain C (-C).,
    as racemates or enantiomers, characterized in that the amine of the general formula
    Hon
    X-AG
    where K, whether Ar have the indicated meanings, is reacted with the racemic or optically active acid chlorohydride of the general formula
    SOS1
    N S,
    40
    followed by isolation of the desired product as a racemate or enantiomer.
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    同族专利:
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    IL83066A|1991-01-31|
    PL149903B1|1990-03-31|
    AU7504787A|1988-01-07|
    DK340087A|1988-01-05|
    DE3762861D1|1990-06-28|
    DD263772A5|1989-01-11|
    TNSN87083A1|1990-01-01|
    IE60743B1|1994-08-10|
    FR2601015B1|1988-08-05|
    NO170419C|1992-10-14|
    PT85235A|1987-08-01|
    KR880001681A|1988-04-26|
    CS501387A2|1988-08-16|
    PL149434B1|1990-02-28|
    US4783472A|1988-11-08|
    CS262692B2|1989-03-14|
    PT85235B|1990-03-30|
    IE871767L|1988-01-04|
    SU1588284A3|1990-08-23|
    HUT44791A|1988-04-28|
    FI872931A|1988-01-05|
    NO872779L|1988-01-05|
    ES2015070B3|1990-08-01|
    ZA874814B|1988-03-30|
    JPS6322589A|1988-01-30|
    AT53037T|1990-06-15|
    MA21027A1|1988-04-01|
    BG47498A3|1990-07-16|
    DK340087D0|1987-07-02|
    BG47038A3|1990-04-16|
    NO170419B|1992-07-06|
    GR3000502T3|1991-07-31|
    FR2601015A1|1988-01-08|
    HU198727B|1989-11-28|
    MX7191A|1993-10-01|
    MX173398B|1994-02-28|
    NZ220929A|1989-09-27|
    NO872779D0|1987-07-02|
    CA1294966C|1992-01-28|
    FI84727B|1991-09-30|
    IL83066D0|1987-12-31|
    EP0253711B1|1990-05-23|
    FI872931A0|1987-07-02|
    AU597996B2|1990-06-14|
    FI84727C|1992-01-10|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    FR2541280B1|1983-01-13|1985-06-21|Rhone Poulenc Sante|NEW DERIVATIVES OF 1H, 3H-PYRROLO THIAZOLECARBOXAMIDE-7, THEIR PREPARATION AND THE MEDICINAL PRODUCTS CONTAINING THEM|
    US4500532A|1983-03-03|1985-02-19|Usv Pharmaceutical Corporation|1--1,4-dihydropyridines|
    FR2601016B1|1986-07-04|1988-10-07|Rhone Poulenc Sante|NOVEL 1H, 3H-PYRROLO THIAZOLE DERIVATIVES, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM|FR2601016B1|1986-07-04|1988-10-07|Rhone Poulenc Sante|NOVEL 1H, 3H-PYRROLOTHIAZOLE DERIVATIVES, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM|
    FR2617484B1|1987-07-02|1989-10-20|Rhone Poulenc Sante|PROCESS FOR THE PREPARATION OF ACID-3 1H-3H-PYRROLOTHIAZOLECARBOXYLIQUE-7 DEXTROGYRE|
    FR2644456B1|1989-03-17|1991-07-05|Rhone Poulenc Sante|NOVEL 1H, 3H-PYRROLOTHIAZOLECARBOXAMIDE-7 DERIVATIVES, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM|
    JP3061631B2|1989-10-11|2000-07-10|山之内製薬株式会社|Novel heterocyclic compound and method for producing the same|
    FR2662606A1|1990-06-01|1991-12-06|Rhone Poulenc Sante|Pharmaceutical compositions for the treatment of ventricular fibrillation and of angina pectoris including unstable angina, containing N--3--1H,3H-pyrrolo[1,2-c]thiazole-7-carbo xamide|
    FR2687574B1|1992-02-25|1995-05-05|Rhone Poulenc Rorer Sa|NEW THERAPEUTIC APPLICATION OF PYRIDYLPYRROLOTHIAZOLE CARBOXAMIDE DERIVATIVES.|
    GB9207645D0|1992-04-08|1992-05-27|Smithkline Beecham Corp|Methods|
    EP1503986B1|2001-12-21|2015-09-30|Cytokinetics, Inc.|Compositions and methods for treating heart failure|
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    EP2328896B1|2008-07-23|2013-10-23|Vertex Pharmaceuticals Incorporated|Tri-cyclic pyrazolopyridine kinase inhibitors|
    US8569337B2|2008-07-23|2013-10-29|Vertex Pharmaceuticals Incorporated|Tri-cyclic pyrazolopyridine kinase inhibitors|
    MX2011000839A|2008-07-23|2011-04-05|Vertex Pharma|Pyrazolopyridine kinase inhibitors.|
    CA2732765A1|2008-08-06|2010-02-11|Vertex Pharmaceuticals Incorporated|Aminopyridine kinase inhibitors|
    CN102459259A|2009-05-06|2012-05-16|沃泰克斯药物股份有限公司|Pyrazolopyridines|
    CN102869664A|2010-01-27|2013-01-09|沃泰克斯药物股份有限公司|Pyrazolopyrimidine kinase inhibitors|
    WO2011094273A1|2010-01-27|2011-08-04|Vertex Pharmaceuticals Incorporated|Pyrazolopyridine kinase inhibitors|
    EP2550272A1|2010-01-27|2013-01-30|Vertex Pharmaceuticals Incorporated|Pyrazolopyrazine kinase inhibitors|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    FR8609728A|FR2601015B1|1986-07-04|1986-07-04|NOVEL 1H, 3H-PYRROLOTHIAZOLE DERIVATIVES, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM|
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