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    • 专利摘要:
    Neue Imidazolderivate der allgemeinen Formel in der A und B zusammen mit den beiden dazwischenliegenden Kohlenstoffatomen eine Gruppe der Formel wobei der Phenyl- und Pyridinring gegebenenfalls substituiert sein kann, R, eine Alkansulfonyloxy-, Trifluormethansulfonyloxy-, Alkansulfonylamino-, Trifluormethansulfonylamino-, N-Alkylalkansulfonylamino-, N-Alkyl-trifluormethansulfonylamino-, Alkylsulfenylmethyl-, Alkylsulfinylmethyl- oder Alkylsulfonylmethylgruppe, eine durch eine Hydroxy-, Alkoxy-, Amino-, Alkylamino- oder Dialkylaminogruppe substituierte Carbonylgruppe, eine durch eine Amino-, Alkylamino-, Dialkylamino- oder cyciische iminogruppe substituierte Sulfonylgruppe, wobei eine Methylengruppe in 4-Stellung durch ein Schwefel- oder Sauerstoffatom ersetzt sein kann, eine Nitro- oder Cyangruppe, R2 eine Alkyl-, Alkoxy- oder Dialkylaminogruppe und R3 ein Wasserstoffatom oder eine Alkoxygruppe bedeuten, deren Tautomere und deren Säureadditionssalze, insbesondere deren physiologisch verträgliche Säureadditionssalze mit anorganischen oder organischen Säuren, welche wertvolle pharmakologische Eigenschaften aufweisen, insbesondere eine Wirkung auf die Kontraktilität des Herzens. Die neuen Verbindungen können nach für analoge Verbindungen üblichen Verfahren hergestellt werden.
    公开号:SU1316559A3
    申请号:SU833606327
    申请日:1983-06-21
    公开日:1987-06-07
    发明作者:Хауэль Норберт；Аустель Фолкхард；Хейдер Иоахим；Рейффен Манфред；Дидерен Вилли
    申请人:Др.Карл Томэ.Гмбх (Фирма)；
    IPC主号:
    专利说明:

    This invention relates to a process for the preparation of novel imidazole derivatives with valuable pharmacological properties.
    The purpose of the invention is the synthesis of new compounds with valuable properties.
    Example 1. 2- (2 -Methoxy-4-methanesulfonylaminophenyl) -imidazo-4,5-c3-pyridine.
    5.45 g (50 mmol 5 of 3,4-diaminopiridine and 12.25 g (50 mmol) of 2-methoxy-4-methanesulfonylaminobenzoic acid are triturated together in 300 ml of phosphorus hydroxide and the resulting 4-amHo-3- (2 -methoxy-4-methanesulfonyl-aminobenzoylamino) -pyridine, heated under reflux for 4 hours. Excess phosphorus oxychloride is then distilled off, 500 ml of water is added to the residue and the pH is adjusted to 8 with concentrated ammonia. The insoluble components are filtered and the filtrate is saturated with sodium chloride, and a crude product is released, which is subjected to chromatography (800 g of alumina, eluent dichloromethane with 5-10%; ethanol). 4.8 g (25.2% of theoretical) of the desired product are obtained. mp. 5 250 ° C.
    Calculated,%: C, 52.81; H 4.43; N 17.60.
    C |, (318.4)
    Found,%: C 52.61; H 4.63; N 17.35.
    H-NMR spectrum (DMCO-d / CDjOD), S, ppm: 3.2 (s, 2H); 4.1 (C, 3N); 6.9-7.3 (m, 2H); 7.5-7.8 (m, 1H); 8.2-8.5 (m, 2H); 8.9-9, .0 (broad s, 1H).
    Similarly, 2- (2-methoxy 4 -N-methylmethanesulfonylaminophenyl) - imidazo-4,5-c-pyridine is obtained from 3,4-diaminopyridine and 2-methoxy-4-N-methylmethanesulfonyl aminobenzoic acid. 19.8% yield from theoretical, So pl. s.250 ° C.
    Calculated,%: C 54.20; H 4.85; N 16.86.
    C, H ,,, S (332.4)
    Found,%: C 54.47; H 4.91; N 16.62.
    H-NMR spectrum (DMCO-dfe / CDjOD), S, ppm: 3.1 (s, 3N); 3.4 (s, 3N); 4.1 (s, 3N); 6.9-7.3 (m, 2H); 7.5-7,
    (m, 1H); 8.2-8.5 (m, 2H); 8.9-9.0 (broad s, 1H).
    Similarly, they receive. 2- (2-methoxy-4 -Y-ethylmethanesulfonylaminophenyl) -imidazo-4,4-c-pyridine from 3,4-diaminopyridine and 2-methoxy-4-N-ethylmethanesulfonyloxybenzoic acid. Yield 16.9% of theoretical
    Calculated,%: C 55.47; H 5.24; N 16,18. C, H | gN, 0, S (346.40)
    Found,%: C 55,58; H 5.31; N 15.92. .
    Spectrum H-NMR (DCMO-d / CD CD) J, h / mpn: 1.0-1.3 (t, 3N); 3.1 (s, ZN); 3.6-4.0 (KB, 2H); 4.1 (s, 3N); 6.9 - 7.3 (m, 2H); 7.5-7.8 (m, 1H); 8.2 - 8.5 (m, 2H); 8.9-9.0 (broad s, 1H). EXAMPLE 2: 2- (2 -Methoxy-4-methanesulfonylaminophenyl) -imidazo-4,5-c3-pyridine.
    Prepared analogously to Example 1 from 2,3-diaminopyridine and 2-methoxy-4-methanesulfonipaminobenzoic acid. The output of 57.3% of theoretical, So pl. 236-238 ° C. R. 0.50 (snickel, solvent — methylene chloride / ethanol 19/1).
    PRI me R 3. 8- (2 -Methoxy-4-methanesulfonylaminophenyl) -purine. Prepared in analogy to example 1 from 4,5-diaminopyrimidine and 2-methoxy-4-methanesulfonyl miobenzoic acid. Output 40.75% of theoretical, so pl. 237-238 C.
    Calculated,%: C, 48.89; H 4.10; N 21.93; S 10.04. ; C ,, H ,, N, 0, S
    Found,%: C 48.81; H 4.37; N 21.88; S 9.95.
    .
    PRI me R 4. 2- 2 -Methoxy-4 - K-metnmethanesulfonylaminophenyl) -imidazo-4,5-L-pyridine,
    Prepared analogously to Example I from 2,3-diaminopyridine and 2-methoxy-4-N-methylmethanesulfonylaminobenzoic acid. The output of 57.2% of theoretical, so pl. 238-240 s.
    Calculated,%: C 54.20; H 4.85; N 16.86; S 9,65
    C, 5K, (332.4)
    Found,%: C 54.20; H 4.91; N 16.68; S 9.86,
    PRI me R 5, 8- (2 -Methoxy-4 - N-methylmethanesulfonylaminophenyl) -purine.
    Prepared analogously to example 1 from 4,5-diaminopyrimidine and 2-methoxy-4-N-methylmethanosulfonoclaminobenzoic
    3
    acid. The output of 45.5% of theoretical, so pl. 250 ° C.
    . Calculated,%: C 50.44; H 4.54; N 21.01; S 9,62 /
    C, 5N, 0, S (333.4)
    Found,%: C 50.15; H 4.77; N 20.77; S 9.50.
    EXAMPLE 6. 2- (3-methoxy-4-methanesulfonylaminophenyl) -imidazo-4,5-b-pyridine.
    Prepared analogously to Example 1 from diaminopyridine and Z-methoxy-4-methane sulfonylaminobenzoic acid. The output of 21.4% of theoretical, so pl. 250 C.
    Calculated,%: C, 52.81; H 4.43; N 17.60; S 10.07.
    C, K ,,, S (318.4)
    Found,%: C 52, bb; H 4.46; N 17.94: s 10.10.
    Example 7. 8- (3 -Methoxy-4-methanesulfonylaminophenyl) -purine.
    Prepared analogously to example 1 of 4,5-diaminopyrimidine and 3-methoxy-4-methanesulfonylaminobenzoic acid. The output of 11.2% of theoretical, so pl. 250 ° C.
    Calculated,%: C, 48.89; H 4.10; N 21.93; S 10.04.
    q. (319.35)
    Found,%: C 48.31; H 4.45; N 21.74; S 10.80.
    Example8. 2- (3 -Methoxy-4-N-methylmethyl anhydhenylamine ofphenyl) -imazo-4,5-c-pyridine.
    Prepared analogously to example 1 from 2,3-diaminopyridine and 3-methoxy-4-N methylmethanesulfonylaminobenzoic acid. Output 38.8% of theoretical, so pl. 250 C.
    Calculated,%: C 54.20; H 4.85; N 16.85; S 9.65.
    C, 5K, gN40, S (332.39)
    Found,%: C 54.59; H 5.22; N 16.57; S 9.55.
     meper 9. 8- (3 -Methoxy-4 - K-methylmethanesulfonylaminophenyl) -purin.
    Prepared analogously to example 1 from A, 5-diaminopyridine and 3-methoxy-4-N-methylmethanesulfonylaminobenzoic acid. Output 9.6% of theoretical, so pl. 250 ° C.
    Calculated,%: C 50.44; H 4.54; N 21.00; S 9.62.
    C. (333.38)
    Found,%: C 50.71; H 5.10; N 20.58; S 9.59.
    559 .4
    Example 10. 2- (2, -Methoxy-4-methanesulfonylaminophenyl) benzimidazole.
    Prepared analogously to example 1 of 5 ortho-phenylenediamine and 2-methoxy-4-methanesulfonylaminobenzoic acid, Yield 23.6% of theory, mp, 250 ° C.
    Calculated,%: C 56.76; H 4.76; O N 13.24; S 10,10
    C, 1, H, Oz5 (317.38)
    Found,%: With 56,40; H 4.61; N 12.96; S 10.27.
    Example 11. 2- (2 -Methoxy-4-5 N-methylmethanesulfonylaminophenyl) -benzimidazole.
    Prepared analogously to Example 1 from ortho-phenylenediamine and 2-methoxy-4-0 K-methylmethanesulfonylaminobenzoic acid. The output of 21.7% of theoretical, so pl. 250 C.
    Calculated,%: C 57.99; H 5.17; N 12.68; S 9.68 5 C, H ,, H, 0, S (331.40)
    Found,%: C 57.98; H 4.96; N 12.79; S 9,53.
    Example 12. 8- (2 -Methoxy-4 N-ethylmethanesulfonylaminophenyl) -poo
    rin
    Prepared analogously to example 1 from 4,5-diaminopyrimidine and 2-methoxy-4-N-methylmethanesulfonylaminobenzoic acid. The output of 13.8% of theoretical, so pl. 246-248 c.
    Calculated,%: C, 51.85; H 4.93; N 20.16; S 9.23
    C, 5H, K50s5 (347.41)
    Q Found,%: C 51.83; H 4.78 ;, N, 19.90; S 9.46.
    Spectrum H-YANR (DMCO-dg / CD OD), ppm: 1.0-1.3 (t, 3N); 3.1 (s, ZN); 3.6-4.0 (KB, H); 4.1 (s, 3N); 7.1-7.3 (m, 2H); 8.2-8.4 (d, W); 8.8 (s, 1H); 9.0 (s, H).
    PRI me R 13. 5-methoxy-2- (2-methoxy-4-methanesulfonylaminophenyl) benzimidazole.
    0 Prepared analogously to example 1 from 4-methoxy-ortho-phenylenediamine and 2-methoxy-4-meta-acid-aminobenzoic acid. The output of 28.8% of theoretical, t, pl. 195-198 ° C.
    5 Calculated,%: C, 55.32; H 4.93; N 12.10; S 9.23.
    C, H ,, (347.40) Found,%: C 55.54; H 5.34; N 11.93; S 8,70.
    51
    Example 14. 5-Chloro-2- (2-methy hydroxy-4-methanesulfonylaminophenyl) -benzimidazole.
    Prepared analogously to example 1 from 4-hlrr-ortho-phenylenediamine and 2-methyloxy-4-methanesulfonylaminobenzoic acid. The output of 43.8% of theoretical, so pl. 230-232 C.
    Calculated,%: C, 51.21; H 4.01; N 11.94; C1 10.08; 9, l.
    C, 5R, 4C1N, 0, S (351.82)
    Found,%: C 51.27; H 4.02; N 11.87; C1 10.15; S 9.00.
    Example 15. 5-Chloro-2- (2-meth o xi-4 -N-methylmethanesulfonylaminophenyl) -benzimidazole.
    Prepared analogously to Example 1 from 4-chloro-ortho-phenylenediamine and 2-met-hydroxy-4-K-methylmethanesulfonylaminobenzoic acid. Yield 28.8% off. theoretical, so pl. 191-192 C.
    Calculated,%: 52.53; H 4.41; N 11.49; C1 9.69; S 8,76
    С, Н, С1К, ОЭЗ (365.85)
    Found,%: C 52.95; H 4, N 11.45; C1 9.86; S 8,82.
    PRI me R 16. 2- (2 -Methoxy-4-methylthiomethylphenyl) -imidazo-4,5-bJ-pyridine.
    Prepared analogously to example 1 from 2,3-diaminopyridine and 2-methoxy-4-methylthiomethylbenzoic acid. Output 35.1% of theoretical, so pl. 148-149 C.
    Calculated,%: C 63.14; H 5.30; N 14.73; S 11.24
    CisKi N O S (285.35)
    Found,%: C 62.72; H 5.53; N 14.47; S 10.84.
    Example 17. 8- (2 -Methoxy-4-methylthiomethylphenyl) -purine.
    Prepared analogously to Example 1 from 4,5-diaminopyrimidine and 2-methoxy-4-methyl 1-benzoic acid. The output of 31.4% of theoretical, so pl. 194-196 ° C.
    Calculated,%: C 58.72; H 4.93; N 19.57
    . S (286.36)
    Found,%: C 58.48; H 4.87; N 19.29.,
    Example 18, 2- (2 -Methoxy-4-cyanophenyl) -imide h, 5-LJ-pyridine,
    3.1 g of 2,3-diaminopyridine and 5.0 g of 2-methoxy-4-cyanbenzoic acid are triturated in 50 ml of phosphorus oxychloride and the resulting 2-amio-3- (2 methoxy-4-cyanbenzoylamino) -pyridine B, 6
    It is heated for 0.5 h with an o6patHbiM refrigerator. After cooling, the reaction mixture is treated with ice water. The precipitate formed is washed with water and dried in an air circulation chamber dryer at 60 ° C. After this drying, the product contains another 1/2 mol of hydrochloric acid and 1/2 mol of water. Yield 6.3 g (80% of theoretical), so pl. 214-216 with (decomposition). For 0.5 mol HC1 and 0.5 mol H, .0: Calculated,%: C 60.59; H 4.18; N 20.19; C1 6.38.
    Found,%: C 60.85; H 4.15; N 20; 48; C1 6.35.
    Example 19. 8- (2 -Methoxy-4-cyanophenyl) -purine.
    Receive analogously to example 18
    from 4,5-diaminopyrimidine (crystalline from, dihydrochloride and 1 mol of sodium chloride) and 2-methoxy-4-cyanobenzoic acid. Output 0.7 g (.20% of theoretical), so pl. 271-272 ° С (from
    methanol).
    Calculated,%: C 62.14; H 3.61; N 27.88.
    Found,%: C 62.34; H 3.69; N 27.62.
    Example 20. 2- (2 -Dimethylamino-4-nitrophenyl) -imidazo-4,5-b-pyridine.
    6.3 g of 2-dimethylamino-4-nitrobenzoic acid and 5.43 g of 2,3-diaminopyridine dihydrochloride are triturated, 125 ml of phosphorus oxychloride are added and the resulting 3-amino-2- (2-dimethylamino-4-nitrobenzene) - but) -pyridine is heated for 2 hours
    with reflux. Then, excess phosphorus oxychloride in vacuum is distilled off and ice water is added to the residue. Then the neutron, alizuk) t ammonia. Bristled solid product
    purified by chromatography on a column of silica gel (the eluent is first methylene chloride, then methylene chloride / ethanol 50: 1-25: 1). Output 2.2 g (26% of theoretical),
    m.p. 208-210 C.
    Calculated,%: C 59.36; H 4.63; N 24.72.
    Found,%: C 59.40; H 4.50; N 25.10,
    Example 9: 5-nitro-2- (2-methoxy-4 -Y-methylmethanesulfonamine aminophenyl) benzimidazole hydrochloride, Prepared analogously to example 1 of 4-nitro-1,2-fench-1-di-diamine and 2-methoxy- 4-N-methylmethanesulfonylaminobenoic acid. The output of 52.1% of theoretical, so pl. 241-2DZ ° C.
    Calculated,%: C, 46.55; H 4.15; N 13.56; S 7.77; C1 8.58.
    CifeKibN O S-HCl (412.87)
    Found,%: C 46.75; H 3.94; N 13.68; S 7.72; C1 .8,29.
    EXAMPLE 22 5-Methoxy-2- (2-methoxy-4-N-methylmethanesulfonyl nophenyl) benzimidazole.
    Prepared analogously to example 1 from 4-methoxy-1,2-phenylenediamine and 2-methoxy-4-K-2-methoxy-sulfonylaminobenzoic acid. The output of 33.7% of theoretical, so pl. 194-19b with.
    Calculated,%: C 56.49; H 5.30; N 11.63; S 8.87.
    C, H ,, N, 04S (361.43)
    Found,%: With 56.49; H 5.40; N 11, 73; S 8,84.
    PRI me R 23. 5-Trifluorophenyl-2- (2-methoxy-4-N-methylmethanesulfonylaminophenyl) benzimidazole.
    Prepared analogously to example 1 of 4-trifluorometh-1-1,2-phenylenediamine and 2-methoxy-4-N-methylmethanesulfonyl nobenzoic acid. Output 6.7% of theoretical, so pl. 222-225 C.
    Calculated,%: C 51.12; H 4.04; N 10.52; S 8.02.
    C, H, gF, N, 0, S (399.41)
    Found,%: C-51.34; H 4.38; N 10.28; S 8.47.
    EXAMPLE 24 5-Trifluoromethyl-2 (2-methoxy-4-methanesulfonylaminophenyl) benzimidazole.
    Prepared analogously to example 1 from 4-trifluoromethyl-1,2-phenylenediamine and 2-methoxy-4-methanesulfonylaminobenzoic acid. The output of 24.9% of theoretical, so pl. .
    Calculated,%: C 49.87; H 3.66; N 10.90; S 8.32.
    C, gK, /, N, 0, S (385.33)
    Found,%: C 49.64; H 3.89; N 10.65; S 8.34.
    EXAMPLE 25 5-Nitro-2- (2-methoxy-4-methanesulfonyl-amino-phenyl) -benzimidazole dihydrochloride.
    Prepared analogously to example 1 from 4-nitro-1,2-phenylenediamine and 2-met-hydroxy-4-m-tansulfonyl-aminobenzoic acid. Output 14.0% of theoretical, so pl. 240-243 ° C.
    Calculated,%: C 39.74; .N 4.00; N 12.36.
    C, 5HKN, OyS Hj, 0-2HCl (453.33)
    Found,%: C 39.56; H 4.06; N 12.40. ..
    PRI me R 26. 5,6-Dimethyl-2- (2-methoxy-4-N-methylmethanesulfonyl-aminophenyl) benzimidazole.
    Receive analogously to example I of
    4,5-dimethyl-1,2-phenylenediamine and 2methoxy-4-K-methylmethanesulfonylaminobenzoic acid. Yield 52.3%
    from theoretical, so pl. 235-238 C.
    Calculated,%: C 60.14; H 5.88; N 1 1, 69; S 8.92.
    C, gH ,, N, 0, S (359.46)
    Found,%: C 59.80; H 5.68; N P, 75; S 8,86.
    Example 27. 5,6-Dimethyl-2- (2-methoxy-4-methanesulfonylaminophenyl) -benzimidazole semihydrochloride.
    Prepared analogously to Example 1 from 4,5-dimethyl-1,2-phenylenediamine and Z-methoxy-4-methanesulfonylaminobenzoic acid. The output of 25.6% of theoretical, so pl. 148-151 ° C.
    Calculated,%: C 56.14; H 5.54; N 11.55.
    ,, N, 0, S .1 / 2HC1 (363.67)
    Found,%: C 56.26; H 5.76; N 1G, 68.
    Example 28. 5,6-dimethoxy-2- (2-methoxy-4 -N-methylmethanesulfonylaminophenyl) benzimidazole hydrochloride
    Prepared analogously to example 1 of 4,5-dimethoxy-1,2-phenylenediamine and 2-methoxy-4-N-methyl-methanoyl sulfonate aminobenzoic acid. Yield 21% of theoretical, tpl, 250 C.
    Calculated,%: C 50.52; H 5.18; N 9.82. C | gHj, N, 05S-KCl (427.93)
    Found,%: C 50.30; H 5.10; N 9.89.
    Example 29. 5,6-Dimethoxy-2- (2-methoxy-4-methanesulfonylaminophenyl) benzimidazole.
    Prepared analogously to Example 1 from 4,5-dimethoxy-1,2-phenylenediamine and 2-methoxy-4-methanesulfonylaminobenzoic acid. Output 27.8% of the theoretical, so pl. 250 ° C.
    Calculated,%: C 54.09; H 5.07; N P, 13.
    C, H ,, N, 05S. (377.49) Found,%: C 53.84; H 5.32; N 10.78.
    Example 30. 5-Methoxycarbonyl-2- (2-methoxy-4-methanesulfonyl-aminophenyl) benzimidazole.
    Prepared analogously to example 1 from 4-methoxycarbonyl-1,2-phenylenediamine and 2-methoxy-4-methanesulfonylaminobenzoic acid. The output of 46.3% of theoretical, so pl, 246-248 C.
    Calculated,%: C 54.39; H .4.56; N 11.19. . C ,, H, 7N, 05S (375.41).
    Found,%: C 53.98; H 4.72; N 10.93. ,
    Example 31.5-Fluoro-2- (2-meth- hydroxy-4-methanesulfonylaminophenyl) -benzimidazole.
    Prepared analogously to Example I from 4-fluoro-1,2-phenylenediamine and 2-methanoxy-4-methanesulfonylaminobenzoic acid. The output of 67.3% of theoretical, so pl. 254-256 ° C.
    Calculated,%: C, 53.72; H 4.20; N 12.53; S 9,56.
    C | 5H ,, FN, 0, S (335.37)
    Found,%: C 53.83; H 4.87; N 12.06; S 9.25.
    PRI me R 32. Hydrochlorine 6-chloro-2- (2-methoxy-4-methanesulfonylaminophenyl) -imidazo-4,5-b-pyridine.
    Prepared analogously to example 1 from 5-chloro-2,3-diaminopyridine and 2-methanoxy-4-methanesulfonylaminobenzoic acid. The output of 28.3% of theoretical, so pl, 250 ° C
    Calculated,%: C 43.19; H 3.62; N 14.39.
    C, 4H ,, C1N O S-HC1 (389.3)
    Found,%: C 43.34; H 4.05; N 14.80.
    EXAMPLE 33, 6-Methyl-2- (2 -meoxy-4-methanesulfonylaminophenyl) - imidazo-4,5-b-pyridine.
    Prepared analogously to example 1 from 5-methyl-2,3-diaminopyridine and 2-methyroxy-4-methanesulfonylaminobenzoic acid. Output 42.2% of theoretical, so pl. 253-25b.
    Calculated,%: C 54.20; H 4.85; N 16.86
    C. (332.4)
    Found,%: C 53.91; H 4.97; N 1b, 51.
    H-NMR spectrum (DMCO-dfe / CDjGD), S, ppm: 2.5 (s, 3N); 3.2 (s, 3N) 4.1 (s, 3N); 6.9-7.2 (m, 2H); 7.8 (broad s, 1H); 8.2-8.4 (m, 2H).
    In a similar manner, 6-methyl-2- (2-methoxy-4 -N-ethylmethanesulfonyl-aminophenyl) -imidazo-4,5-1-pyridine is obtained from 5-methyl-2, 3-diaminopyridine and
    2-methoxy-4-ethylmethanesulfonylaminobenzoic acid. Output 42.2% of theoretical, so pl. 253-256 S.
    Calculated,%: C 54.20; H 4.85; N 16.86.
    C ,, H ,,, S (332.4)
    Found,%: C 53.91; H 4.97; N 16.51.
    H-NMR spectrum (DMCO-dJCD OD), 8, h, ppm: 2.5 (s, 3N); 3.2 (s, AN); 4.1 (s, 3N); 6.9-7.2 (m, 2H); 7, .8 (broad s, 1H); 8.2-8.4 (m, 2H).
    EXAMPLE 34 6-Methyl-2- (2-methoxy-4-N-methylmethanesulfonylaminophenyl) -imidazo-4,5-b-pyridine.
    Prepared analogously to example 1 from 5-methyl-2,3-diaminopyridine and 2-metroxy-4-K-methylmethanesulfonylaminobenzoic acid. The output of 46.2% of theoretical, so pl. 246-248 With,
    Calculated,%: C 55.48; H 5.24; N 16.18; S 9,26.
    C, gK ,, S (346.4)
    Found,%: C 55.26; H 5.28; N 16.35; S 9.14,
    EXAMPLE 35. 2- (2 -Methoxy-5-methanesulfonylaminophenyl) -imidazo-4,5-bJ-pyridine.
    Prepared analogously to example 1 from 2,3-diaminopyridine and 2-methoxy-5-methanesulfonylaminobenzoic acid. The output of 14.2% of theoretical, so pl, 250 ° C
    Calculated,%: C, 52.81; H 4.43; N 17.60; S 10.07.
    C ,, K ,, N, 0, S (318.4) Found,%: C 52.73; H 4.63; N 17.25; S 10.79.
    PR-memer 36. 5-hydroxy-2- (2-meth-hydroxy-4-methanesulfonylaminophenyl) -benzimidazole.
    1.6 g (10 mmol) of 4-OXY-1,2-phenylenediamine and 4.9 g (20 mmol) of 2-methoxy-4-methanesulfonylaminobenzoic acid are triturated in 80 ml of phosphorus oxychloride to form 2-amino- 1- (2-methoxy-4-methanesulfonylaminobenzoyl-amino) -oxybenzyl is stirred under reflux for 90 minutes. Then the dark solution is decanted from the undissolved components, phosphorus oxychloride is distilled off in vacuum and 10 g of crushed ice are carefully added to the residue. sucked off and purified by chromatograph
    Phy (250 g silica gel, eluent methylene chloride with 5% ethanol). Output 9.7% of theoretical, mp: decomposition at 150 C.
    Calculated,%: C 54.04; H 4.53; N 12.60; S 9.62.
    C, 5K ,, N, (333.38)
    Found,%: C 54.36; H 4.91; N 12.31; S 9.77,
    Example 37 2- (2-Methoxy-4-methanesulfonylaminophenyl) -6-hydroxyimidazo-4,5-b-pyridine.
    Prepared analogously to Example 1 from 2,3-diamino-5-acetoxypyridine and 2-methoxy-6-methanesulfonylaminobenzoic acid. The product is purified in a clikel gel column (eluent is first methylene chloride, then methylene chloride / ethanol 50: 1-9: 1). The output of 0.06 g (69% of theoretical), so pl. 225 C (decomposition), mass spectrum: molar mass 334.
    And p-meper 38. 2- (2 -Methoxy-4 methylthiomethylphenyl) -imidazo-4,5-cJ pyridine.
    Prepared analogously to example 1 from 3,4-diaminopyridine and 2-methoxy-4-methylthiomethylbenzoic acid. The output of 15.8% of theoretical.
    Calculated,%: C 63.13; H 5.30; N 14.73
    C ,, N, 5SOZ S (285.35)
    Found,%: C 62.91; H 4.99; N 14.48.
    H-NMR spectrum (DMCO-d6 / CD, OD), fi, ppm: 2.1 (s, 3N); 3.7 (s, 2H) 4.1 (s, 3N); 6.9-7.3 (m, 2H); 8.0- 8.7 (m, 3N); 9.2-5-9.35 (broad s, 1H).
    EXAMPLE 39. 2- (2 -Methoxy-4 methyl trifluoromethanesulfonylaminophenyl) -imidazo-4,5-b-pyridine.
    Prepared analogously to Example 1 from 2,3-diaminopyridine and 2-methoxy-4-N-methyl trifluoromethanesulfonylaminobenzoic acid. The output of 12.1% of theoretical, so pl. 250 sec.
    Calculated,%: C, 46.63; H 3.39; N 14.50,
    C ,,. H, jF, N, 0, S (386.35)
    Found,%: C 46,93; H 3.48; N 14.11,
     Example 40. 2- (2-methoxy-4 -N-ethyl trifluoromethanesulfo-n-1-aminophenyl) benzimidazole hydrochloride.
    Prepared analogously to example 1 from ortho-phenylenediamine and 2-methoxy-4-K-ethyl trifluoromethanesulfonyl aminoben 12
    zoic acid. The output of 24.7% of theoretical.
    Calculated,%: C, 46.84; H 3.93; N 9.64 C ,, HnClFiN, 0, S (435.85)
    Found,%: C 47.12; H 4.01; N 9.33.
    PRI me R 41. 2- (2-methoxy-4-trifluoromethanesulfonylaminophenyl) benzimidazole hydrochloride.
    Prepared analogously to Example 1 from ortho-phenylenediamine and 2-methoxy-4-trifluoromethanesulfonylaminobenzoic acid. The output of 18.3% of theoretical, so pl. 220 ° C.
    Calculated,%: C, 44.18; H 3.21; N 10.31.
    C, yK ,, ClF, N, 0, S (407.8) Found,%: C 44.33; H 3.17;
    N 10.11.
    Example 42 2- (2-methoxy-4-trifluoromethanesulfonyl-aminophenyl) -imidazo-4,5-bJ-pyridine hydrochloride. Prepared analogously to Example 1 from 2,3-diaminopyridine and 2-methoxy-4-trifluoromethanesulfonyl and benzoic acid. Output 15.1% of theoretical, so pl. 220 ° C.
    Calculated,%: C 41.13; H 2.96; N 13.71.
    C |, H | iClF, N, 0, S (408.8) Found;%: C 40.88; N. N 13.52.
    The following compounds are prepared analogously.
    2- (2 -Methoxy-4-methanesulfonyl-oxyphenyl) benzimidazod, m.p. 197-198 ° C.
    Calculated,%: C 56.59; H 4.43; N 8.80; S 10.07.
    C, 5H ,, (318.34) Found,%: C 56.60; H 4.43; N 8.74; S 10.20. 2- (2 -Methoxy-4-methanesulfonyl. G 1
    hydroxyphenyl) -imidazo- .4,5-bj-pyridine, mp 208-209 ° C.
    Calculated,%: C 52.66; H 4.10; N 13.16; S 10.04, C ,, H ,, N, 0, S (319.3)
    Found,%: C 52.41; H 3.98; N 13.22; S 9.99.
    2- (2, 4-dimethoxy-3-methanesulfonyloxyphenyl) -imidazo-4,5-pyridine hydrochloride, m.p. 202-20b with (decomposition).
    Calculated,%: C, 46.49; H 4.18; N 10.89; C1 9.19.
    C ,, H ,, C1N, 05S (385.83)
    fO
    /five
    20
    131316559
    Found, JS: C 46.83; H 4.13; . N 11.18; S 9.47.
    8- (2 Methoxy-4-methanesulfonyl-hydroxyphenyl) -purine, m.p. 225-227 seconds
    Calculated,%: C, 48.75; H 3.78; N 17.49; S 10.01.
    C ,, H ,, N, 0, S. (320.3)
    Found,%: C 48.52; H 3.72; N 17.25; S 10.00.
    8- (2 -Methoxy-4-ethanesulfonyl-oxyphenyl) -purine, m.p., 195-196 C.
    Calculated,%: C 50.29; And 4.22; N 16.76; S 9.59.
    C „K, (334.4): Found,%: C 50.02; H 4.15; N 16.59; S 9.83.
    2- (2 -Methoxy-4-ethanesulfonyl-xiphenyl) -imidazo-1 4,5-bj-pyridine, m.p. 206-209 ° C.
    Calculated,%: C 54.04; H 4.54; N 12.60; S 9.62.
    C, 5H ,, N, (333.4)
    Found,%: C 54.11; H 4.59; N 12.43; S 9.71.
    2- (2 -Methoxy-3-methanesulfonyl-25 syphenyl) -imidazo-L4,5-b3-pyridine, m.p. 153-155 ° C.
    Calculated,%: C 52.66; H 4.10; N 13.16; S 10.04.
    C ,, H ,, N, (319.3)
    Found,%: C 52.40; H 3.96; N 13.17; S 10.04.
    8- (2 -Methoxy-3-methanesulfonyl-hydroxy-1) -purine, m.p. 187-188 C.
    Calculated,%: C, 48.75; H 3.78; N 17.50; S 10.0 ..
    C, H, TO, 8 (320.3)
    Found,%: C 48.70; H 4.02; N 17.37; S 10.35.
    2- (3 -Methoxy-5-methanesulfonyl-hydroxyphenyl) -purine, m.p. 187-188 C.
    Calculated,%: C, 48.75; H 3.78; N 17.50; S 10.01.
    C, 3H ,, (320.3)
    Found,%: C 48.70; H 4.02; N 17.37; S 10.35.
    2- (3 -Methoxy-5-methanesulfonyl-hydroxyphenyl) -imidazo-G4,5-b-pyridine, m.p. 225-227 ° C.
    Calculated,%: C 52.65; H 4.10; N G3.15; S 10.04.
    C, H ,, N, (319.35)
    Found, -%: C 52.86; H 4.32; N 13.20; -S 9.91
    N, N, 048 (319.3)
    Found,%: C 52.80; H 4.05; N 13.11; S 10.15.
    5-Trifluoromethyl-2- (2-methoxy-4-methanesulfonyloxyfeiyl) benzimidazole, m.p. 138-140 ° C.
    Calculated,%: C 49.74; H 3.39; N 7.25; S 8.30
    ,, F (386.36)
    Na-%,%: C 49.43; H 3.54; N 7.17; .S 8.34.
    5-Methoxy-2- (2-methoxy-4-methane sulfonyl siphenyl) -benzimidazole, so pl. 152-154 C.
    Calculated,%: C 55.16; H 4.63; N 8.04; S 9.20
    C ,, H ,, N, 0, S (348.39)
    Found,%: C 55.38; H 4.78; N 7.94; 8 9.28.
    5-Cyano-2- (2-methoxy-4-methane-sulfonyloxy-phenyl) -benzimidazole, mp.225-227 ° C.
    Calculated,%: C 55.96; H 3.82; N 12.24; 8 9.34
    C, gH ,, (343.37)
    Found,%: C 55.71; H 3.93; N 12.08; 8 9,24.
    2- (2 -Methoxy-4-methylsulfonylmethylphenyl) -imidazo-4,5-bj-pyridine m.p. 224-225 ° C.
    Calculated,%: C, 56.77; H 4.76; N 13.24; S 10,10.
    C, 5H, 5N, 0.8 (317.38)
    Found,%: C 56.23; H 4.78; 35 N 12.97; 8 9.68.
    8- (2 -Methoxy-4-methylsulfonylmethylphenyl) -purine, m.p. 235-237 s.
    Calculated,%: C, 52.82; H 4.43; N 17.60
    C, 4K ,, 8 (318.36)
    Found,%: C 52.74; H 4.60; N 16.81.
    2- (2 -Methoxy-4-methylsulfinylmethylphenyl) -imidazo-4, 5-b-pyridine
    Calculated,%: C 59.78; H 5.02; N 10.64.
    C, 5N, 0.8 (301.38)
    Found,%: C 59.42; H 5.54; N 11.53.
     H-NMF-spectrum (CDC1, / CD, OD), S, ppm: 2.6 (s, 3N); 4.1 (s, 5H); 6.9-7.4 (m, 3N); 7.8-8.0 (m, 1H); 8.2-8.4 (m, 2H).
    8- (2 -Methoxy-4-methylsulfinyl) 30
    40
    45
    50
    2- (3 -Methoxy-4-methanesulfonyl-55 methylphenyl) -purine, R, 0.18 (silica-oxyphenyl) -imidazo-4,5-b-pyridine, m.p. 235-237 s.
    Calculated,%: C 52.66; H 4.10; N 13.16; S 10.04.
    gel, solvent - metnpenchloride / ethanol 9: 1).
     n-NMR spectrum (CDCl1 / CDjOD), ppm: 2.6 (s, 3N); 4.1 (s, 5H);
    fO
    /five
    0
    .
    five
    N, N, 048 (319.3)
    Found,%: C 52.80; H 4.05; N 13.11; S 10.15.
    5-Trifluoromethyl-2- (2-methoxy-4-methanesulfonyloxyfeiyl) benzimidazole, m.p. 138-140 ° C.
    Calculated,%: C 49.74; H 3.39; N 7.25; S 8.30
    ,, F (386.36)
    Na-%,%: C 49.43; H 3.54; N 7.17; .S 8.34.
    5-Methoxy-2- (2-methoxy-4-methanesulfonyl syphenyl) -benzimidazole, m.p. 152-154 C.
    Calculated,%: C 55.16; H 4.63; N 8.04; S 9.20
    C ,, H ,, N, 0, S (348.39)
    Found,%: C 55.38; H 4.78; N 7.94; 8 9.28.
    5-Cyano-2- (2-methoxy-4-methane-sulfonyloxy-phenyl) -benzimidazole, mp.225-227 ° C.
    Calculated,%: C 55.96; H 3.82; N 12.24; 8 9.34
    C, gH ,, (343.37)
    Found,%: C 55.71; H 3.93; N 12.08; 8 9,24.
    2- (2 -Methoxy-4-methylsulfonylmethylphenyl) -imidazo-4,5-bj-pyridine. m.p. 224-225 ° C.
    Calculated,%: C, 56.77; H 4.76; N 13.24; S 10,10.
    C, 5H, 5N, 0.8 (317.38)
    Found,%: C 56.23; H 4.78; 5 N 12.97; 8 9.68.
    8- (2 -Methoxy-4-methylsulfonylmethylphenyl) -purine, m.p. 235-237 s.
    Calculated,%: C, 52.82; H 4.43; N 17.60
    C, 4K ,, 8 (318.36)
    Found,%: C 52.74; H 4.60; N 16.81.
    2- (2 -Methoxy-4-methylsulfinyl-methylphenyl) -imidazo-4, 5-b-pyridine.
    Calculated,%: C 59.78; H 5.02; N 10.64.
    C, 5N, 0.8 (301.38)
    Found,%: C 59.42; H 5.54; N 11.53.
     H-NMF-spectrum (CDC1, / CD, OD), S, ppm: 2.6 (s, 3N); 4.1 (s, 5H); 6.9-7.4 (m, 3N); 7.8-8.0 (m, 1H); 8.2-8.4 (m, 2H).
    8- (2 -Methoxy-4-methylsulfinyl0
    0
    five
    0
    5 Methylphenyl) -purine, R, 0.18 (silicamethylphenyl) -purine, R, 0.18 (silica gel, solvent - metnpenchloride / ethanol 9: 1).
     n-NMR spectrum (CDCl1 / CDjOD), ppm: 2.6 (s, 3N); 4.1 (s, 5H);
    15 316559.6
    7.0-7.3 (m, 2H); 8.3-8.6 (m, 1H); Calculated,%: C 60, AO; H 4.73;
    8.8-9.1 (m, 2H) .N 18.78.
    2- (2 -Methoxy-4 -carboxyphenyl) -Found,%: C 60,11; H 4.82;
    imidazo-4,5-b-pyridine, t.pl., 309-N 18.87,
    ZSH C.5 Hydrochloride 2- (2-methoxy-4-d 205-210 ° C.
    Found,%: C 62., 30; And 4.47; Calculated,%: C 48.84; H 4.65;
    N 15.60. . N 15.19, - C1 9.16; S 8,69,
    Hydrochloride 2- (2-methoxy-4-met- O Found, 7: С 4.8.56; H 4.53;
    hydroxycarbonylphenyl) -imidazo-4, 15.09; C1 9.44; S 8,69.
    pyridine, so pl. 238-239 with (decomposed-Hydrochloride 2- (2-methoxy-4 -menia). Thylaminosulfonylphenyl) -imidazo Calculated,%: C 56.34; H 4,, 5-b-pyridine, so pl. 205-207 seconds
    N 13.14; C1 11.09.15 (decomposition).
    Found,%: C 55.96; H 4.50; Calculated,%: C 46.22; H 4.73;
    N 13.30; C1 11.75. N 15.40; C1 9.75; S 8,81,
    Hydrochloride 2- (2-methoxy-4 -ami-Found; C46.19; H4.86;
    nocarbonnylphenyl) -imidazo-4,5-З3-pi-N 15.00; C1 10.08; S 8.52.
    Ridin, m.p. 280 C.20 Hydrochloride with 2- (2-methoxy-4 -ami) Calculated: C 55.18; H 4.30; nosulfonylphenyl) -imidazo-4, 18.39; C1 11.63.pyridine, m.p. 225 ° C.
    Found,%: C 55.36; H 4.46; Calculated,%: C 45.82; H 3.85;
    N 18.29; C1 11.76. .N 16.44; C1 10.40; S 9.41.
    2- (2 -Methoxy-4-methylaminocarbo-25; Found: C, 45.67; H, 4.11;
    nilphenyl) imid 30- 4,5-b | -pyridine, N 16.24; C1 10.15; S 9.18.
    m.p. 263-265 ° C (from ethanol) .8- (2 -Methoxy-4-aminosulfonyl) Calculated,%: C 63.82; H 5.00; phenyl) -purine, m.p. 270 ° C (decomposition N 19.85. Ing).
    Found,%: C 63.50; H 5.38; 30 Calculated,% C, 47.21; H 3.63;
    N 19,59.N 22,94; S 10.50.
    Hydrochloride 2- (2-methoxy-4-di-Found,%: C 46,95; H 3.68;
    methylaminocarbonylphenyl) -imidazo-N 22.84; S 10.50.
    4,5-b-pyridine, m.p. 232 C (once-hydrochloride 8- (2-methoxy-4-overlay). Es tsh1 aminosulfonylphenyl) -purine.
    Calculated,%: C 57.75; H 5.15; mp. (decomposition).
    N 16.84; C1 10.85. Calculated,%: C 43.88; H 3.97;
    Found,%: C 57.50; H 5.46; N 19.68; C1 9.97; S 9.01.
    N 16.65; C1 10.94. Found,%: C 43.96; H 4.04;
    8- (2 -Methoxy-4 -carboxyfensh1) -40 N 19.67; C1 9.86; , 98.
    purine, m.p. 250 C. 8- (2-methoxy-4-di-hydrochloride Calcd.,%: C 57.78; H 3.73; methylaminosulfonylphenyl) -purine,
    and 20 73.t.pl. 230-234 C.
    Found,%: C 57.40; H 3.85; Calculated,%: C 45.47; H 4.36;
    N20.84. , 45 (2 -Methoxy-4-aminocarbonyl-Found;%: C 45.11; H 4.66;
    Nile) -purin, so pl. 250 ° C.N. 19.26; -C1 9.24; S 8.43,
    Calculated,%: C, 56.86; H 4.50 ;, 8- (2 -Methoxy-4 - (4-morpholines1N 25.85. SulfonylphenylJ-purine, m.p.
    Found,%: C 57.15; H 4.25; 50 Calculated,%: C 51.20; H 4.56;
    N 25.61.N. 18.66; S 8.54,
    8- (2 -Methoxy-4-methylaminocarbo-Found;%: C 51.00; H 4.56;
    nilphenyl) -purine, so pl. .N 18.40; S 8.80,
    Calculated,%: C 59.36; H 4.63; 8- (2 -Methoxy-4-n-butylaminosulN 24.72.5 fonylphenyl) -purine, m.p. 212-214 s.
    Found,%: C 58.98; H 4.66; Calculated,%: C 53.17; H 5.30;
    N 24.55.N 1.38; 38.87,
    8- (2 -Methoxy-4 -zutoxycarbonyl-Found;%: C 53.43; H 5.46 ;.
    phenyl) -purine, so pl. 210-212 s. N 19.00; S 8.51.
    17131655918
    2- (2 -Dimethylamino-4-methanesul-Calculated,%: C, 49.87; H, 4.67;
    Fonylaminophenyl) -imidazo-4,5-cJ-nH-N 10.26; S 7.83.
    Ridin, mp. 265-267 ° C. C, H, N ,,, 6 (409.42).
    Calculated,%: C 54.38; H 5.17; Found: C 50.32; H 4.70;
    N 21.14; S 9.66.5 N 10.49; S 7.85.
    Found,%: C 54.10; H 5.08; 5-Methyl-2- (2-methoxy-4-methane-N2I, 03; S9,12. Sulfonyloxyphenyl) benzimidazole,
    2- (2 -Dimethylamino-4-methanesulfo-mp. 130-133 ° C.
    niloxyphenyl) -imidazo-G4,5-pyr-Calculated,%: C 57.81; H 4.85;
    din, so pl. 197-199 ° C. . N 8.43; S 9.65.
    Calculated,%: C 54.22; H 4.85; C, H, BY, (332.4)
    N 16.86; S 9.67. Found,%: C 57.66; H 5.04;
     Found,%: C 54.31; And 4.89; N, 8.40; S 9,54.
    N 16.61; S 9.47. 5-Fluoro-2- (2-methoxy-4-methane 5: -Acetamino-2- (2-methoxy-4-me-5 sulfonyloxyphenyl) -benzimidazole,
    tansulfonyloxyphenyl) benzimidazole, mp; 203-204 0. m.p. 220-222 ° C.
    Calculated,%: C 54.39; H 4.56; N 11.19; S 8.54. C, K, N, 0, S (375.41)
    Found,%: C 54.20; H 4.50; N 11.07; S 8.40.
    5,6-Dimethyl-2- (2-methoxy-4-methylsulfonyloxyphenyl) benzimidazole, yield: 39% of theoretical, so pl. 1 75-176 ° C.
    Calculated,%: C 56.02; H 5.53;
    N 7.69.
    CpH ,,, (364.43)
    Calculated,%: C 53.56; H 3.90; N 8.33; S 9,53.
    C. (336.35) 20 Found,%: C 53.40; H 3.97; N 8.75; S 9.61,
    2- (2 -Methoxy-4-trifluoromethane-sulfonyloxyphenyl) -benzimidazole, m.p. 191-193 ° C
    Calculated,%: C, 48.39; H 2.98; N 7.53; S 8.61.
    C, H ,, F, N, (372.3)
    Found,%: C 48.08; H 3.20; N 7.48; S 9.0630 2- (2 -Methoxy-4-trifluoromethane-sulfonyloxyphenyl) -imidazo-4,5-y pyridine, mp. 205-207 ° C.
    Found,%: C 56.02; H 5.80; N 6.98.
    2- (2 -Methoxy-4-methanesulfonyl-oxyphenyl) -imidazo-4,5-c-pyridine, m.p. 208-210 C.
    Calculated,%: C 52.66; H 4.10; N 13.16.
    C ,, H ,, N, (319.35)
    Found,%: C 52.60; H 4.21; N 13.10.
    5-Methoxycarbonyl-2- (2-methoxy-4-methanesulfonyloxyphenyl) benzimidazole, m.p. 121-123 p.
    Calculated,%: C, 51.76; H 4.60; N 7.10.
    C, H, .H ,, 0 (394.42)
    Found,%: C 52.03; H 4.56; N 7.14.
    5-Methanesulfonylamino-2- (2-meth- hydroxy-4-methanesulfonyloxyphenyl) -benzimidazole, m.p. 240 ° C (decomposition).
    Calculated,%: C, 46.70; H 4.16; N 10.21.
    C ,, H ,, (411.47)
    Found: C46.63, H4.25, N 10.16.
    5-Methoxycarbonylamino-2- (2-met-hydroxy-4-methanesulfonyloxyphenyl) benzimidazole, m.p. 140 C (decomposition).
    m.p. 203-204 0.
    Calculated,%: C 53.56; H 3.90; N 8.33; S 9,53.
    C. (336.35) 0 Found,%: C 53.40; H 3.97; N 8.75; S 9.61,
    2- (2 -Methoxy-4-trifluoromethane-sulfonyloxyphenyl) -benzimidazole, m.p. 191-193 ° C
    Calculated,%: C, 48.39; H 2.98; N 7.53; S 8.61.
    C, H ,, F, N, (372.3)
    Found,%: C 48.08; H 3.20; N 7.48; S 9.060 2- (2 -Methoxy-4-trifluoromethane-sulfonyloxyphenyl) -imidazo-4,5-l-pyridine, mp. 205-207 ° C.
    Calculated,%: C 45.05; H 2.70; N And, 26. 5 C ,, K, /, N, (373.3)
    Found,%: C 45.29; H 2.75; N 11.38.
    8- (2-n-propyl-4-methanesulfonyloxyphenyl) -purine, m.p. 214-21b p. 0 Calculated,%: C 54.20; H 4.85; N 16.86.
    C, 5H ,, S (332.4) Found,%: C 54.45; H 4.77; N 17.00.
    5 8- (2 -Methoxy-4-trifluoromethane-sulfonyloxyphenyl) -purine, m.p. 228-229 p.
    Calculated,%: C, 41.72; H 2.42; N 14.97. 0 C, 5H ,, 0, S (374.3)
    Found%: C 41.75; H 2.50; N 15.20.
    8- (2-Ethyl-4-methanesulfonyloxy-phenyl) -purine, m.p. 237-238 C. Calculated,%: C 52.81; H 4.43; N 17.60,
    Ci. (318.4) Found,%: C 53.00; H 4.39; N 17.70.
    19 131655920
    6-Methyl-2- (2-methoxy-4-methane-Calculated,%: C 55.47; H 5.24;
    sulfonypoxyphenyl) -imidazo-4,5-bJ-N 16, 17; S 9, 26.
    pyridine, so pl. 185-187 C.C, bH, 8N, 0, S (346.42)
    Calculated,%: C 54.04; H 4.54; Found: C 55.22; H 5.38;
    N 12.60; S 9.62.5 N 16.00; S 9.24,
    .NjOjS (333.4) Dihydrochloride with 5-amino-2- (2 -methe Found,%: C 54.04; H 4.55; hydroxy-4-methanesulfonylaminophenyl N 12.68; S 9.50. Nofenshen1) -benzimidazole, m.p. 2155-Amino-2- (2-methoxy-4-methanesul217 C.
    Fonyloxyphenyl) -benzimidazole O Calculated,%: C 44.45; H 4.48;
    Mass spectrum: (mol-peak) .N 13.82; S 7.91; C1 17.50,
    Calculated,%: С.54,04; H 4.54; C, 5H, gN, 0, S 2HC1 (405.32)
    N 12.61. . Found,%: C 44.08; H 4.71;
    C ,, K ,, N, 0, S (333.38) N 13.92; S 7.80; Cl 17.75,
    Found,%: C 53.98; H 4.51; -5 5-Aminocarbonyl-2- (2-methoxy-4 N 12,73 methanesulfonyloxyphenyl) -benzimide 5-Oxy-2- (2-methoxy-4-methanesulfene, so pl .: sintering with 185 ° C.
    fonyloxyphenyl) benzimidazole, mp. 2- (2 -Netoxy-4-methylsulfinyl158-160 ° C. methylphenyl) -imidazo-4,5-c-pyridine.
    Calculated,%: C, 53.88; H 4.22; 20 n-NMR spectrum (DMSO-dg / CD, OD),
    N 8.38; S 9.59. 8 ppm: 2.6 (s, MN); 4.1 (s, 5H);
    Ci H NzOfS (334.36) 6.9-7.3 (m, 2H); 8.0-8.7 (m, 3N);
    Found,%: C 54.05; H 4.44; 9.3-9.4 (broad s, 1H).
    N8.10; S9,55,2- (2 -Methoxy-4-methylsulfonyl-5-Methylaminocarbonylamino-2- (2 -25 m), imidazo-C4,5-c-pyridine.
    methoxy-4-methanesulfonyloxyphenyl) -Calculated,%: C 56.77; H 4.76;
    benzimidazole N 13.24.
    Calculated,%: C, 52.30; H 4.65; C. (317.38)
    N 14.35; S 8.21, Found,%: C 56.41; H 4.51;
    With TsDUB (390.43) 30 N 12.78
    Found,%: C 52.15; H 4.83; H-spectrum NMR (DMCO-dg / CDjOD),
    N 14.46; S 7.97.6, ppm: 2.9 (s, 3N); 4.1 (s, 3N);
    5-Aminocarbonylamino-2- (2-marks-4.4 (s, 2H); 7.0-7.4 (m, 2H); 8.0 si-4-methanesulfonyloxyphenyl) -benz-8.6 (m, ZN); 9.2-9.3 (broad s, 1H).
    imidazole, yield: 34.5% of theoretical-35 2- (2 -Methoxy-4-carboxyphenyl) whom .imidazo-4,5-b-pyridine, so pl. 309 Calculated,%: C 51.06; H 4.18; 310 ° C.
    N 14.54; S 8.32. Calculated,%: C 62.45; H 4.12;
    . (376.40) N 15.61.
    Found,%: C 50.81; H 4.16; 40 Found,%: C 62.30; H 4.47;
    N 14.29; S 8.71, N 15.60.
    5-Methylaminocarbonyl-2- (2-marks-Hydrochloride 2- (2-methoxy-4-methy-4-methanesulfonylaminophenkp) -benz-hydroxycarbonylphenyl) gimidazo-t4,5-b3-imidazole, mp. 120-124 ° C. of Pyridin, m. 238-239 C (decomposedCalculated,%: C 54.53; H, 4.85; 45%).
    N 14.96; S 8.56. . . Calculated,%: C 56.34; H 4.41;
    C, H, gN, (374.43) N 13.14; Cl 1 1, 09.
    Found,%: C 54.21; H 4.97; Found: C 55.96; H 4.50;
    N 14.87; S 8.28.N 13.30, Cl 11.75.
    5-Oxymethyl-2- (2-methoxy-4-me-50 8- (2-methoxy-4 -carboxyphenyl) tansulfonylaminophenyl) -benzimidazoloprin, mp, 250 C.
    Calculated Z: C 55.32; H 4.93; Calculated,%: C 57.78; H 3.73;
    N 12.10; S 9.23N 20.73,
    C, BC. N, 0.5 (347.4) Found,%: C 57.40; H 3.85;
    Found,%: C 54.95; H 5.22; 55 20.84.
    N11.79; S9,14.8- (2-Methoxy-4-ethoxycarbonyl 5-AMINO-2- (2-methoxy-4-H-methyl-phenyl) -purine, mp 210-212 ° C.
    methanesulfonylaminophenyl) -benzimide-Calculated,%: C 54.04; H 4.54;
    angry, mp 216-218 ° C.N 12.61.
    21
    Found,%: C 53.98; H 4.51; N 12.73.
    5-Oxy-2- (2-methoxy-4-methane-sulfonyloxy-phenyl) -benzimidazole, t, pl. 158-1 ° C.
    Calculate,%: C, 53.88; H.4.22; N 8.38; S 9.59. , C, 5H ,, N, 05S (334.36)
    Found,%: C 54.05; H 4.44; N 8.10; S 9.55.
    5-Methylaminocarbonylamino-2- (2-methoxy-4-methanesulfonyloxyphenyl) benzimidazole.
    Calculated,%: C, 52.30; H 4.65; N 14.35; S 8.21.
    C ,, H, eN40jS (390.43)
    Found,%: C 52.15; B 4.83; N 14.46; S 7.97.
    5-aminocarbonylamino-2- (2-labels si-4-methanesulfonyloxy) -benz imidazole.
    Calculated,%: C 51.06; H 4.18; N 4.54; S 8.32.
    ,, N, 0, S (376.40)
    Found,%: C 30.81; H 4.16; N 14.29; S 8.71.
    5-Methylaminocarbonyl-2- (2-labels si-4-methanesulfonylaminophenyl) ben imidazole, so pl. 120-124 C.
    Calculated,%: C 54.53; H 4.85; N 14.96; S 8.56.
    ,, N, (374.43)
    Found,% C 54.21; And 4., 97; N 14.87; S 8.28
    5-Oxymethyl-2- {2-methoxy-4-methanesulfonylaminophenyl) -benzimidazo
    Calculated,%: C, 55.32; H A, 93; N 12.10; S 9.23.
    CI. (347.4)
    Found,%: .C 54.95; H 5.22; N 11.79; S 9.14.
    5-amino-2- (2-methoxy-4-N-methyl, methanesulfonylaminophenyl) benzimidazole, m.p. 216-218 s.
    Calculated,%: C 55.47; H 5.24; N 16.17; S 9,26.
    C ,, H, gN, 0, S (346.42)
    Found,%: C 55.22; H 5.38; N 16.00; S 9.24.
    5-Amino-2- (2-methoxy-4-methanesulfonylaminophenyl) - benzimidazole dihydrochloride, m.p. 215-217 C.
    Calculated,%: C, 44.45; H 4.48; N 13.82; S 7.91; C1 17.50
    C..2HC1 (405,32)
    Found,%: C 44.98; H 4.71; N 13.92; S 7.80; C1 17.75.
    131
    6559. 22
    5-Aminocarbonyl-2- (2-methoxy-4-methanesulfonyloxyphenyl) benzimidazole, mp: sintering c.
    . g
    5 Examine the biological properties of the following compounds:
    0
    five
    0
    five
    0
    five
    0
    five
    0
    five
    A - 2- (2-methoxy-4-cyanophenyl) -. imidazo-4,5-b-pyridine;
    B - 2- (2-methoxy-4-aminocarbonylphenyl) -imidazo-4,5-b-pyridine;
    B - 8- (2-methoxy-4-cyanophenyl) -purine;
    G - 8- (2-methoxy-4-aminocarbonylphenyl) -purine:
    D - 2- (2-methoxy-4-methylamino-sulfonylphenyl) -imidazo-4,5-b-pyridine;
    E is 8- (2-methoxy-4-methylamino-sulfonylphenyl) -purine;
    G - 2- (2-methoxy-4-methanesulfonyloxyphenyl) -imidazo-4,5-b pyridine;
    3 - 2- (2-metrxy-4-methanesulfonyloxyphenyl) benzimidazole;
    And - 8- (2-methoxy-4-methanesulfonyloxyphenyl) -purine;
    K 8- (2-methoxy-4-methanesulfonyl-aminophenyl) -purine;
    L - 2- (2-methoxy-4-N-methylmethanesulfonylaminophenyl) -imidazo-4,5-b-pyridine;
    M - 8- (2-methoxy-4-N-methylmethanesulfonylamino-feil) -purine;
    H - 2- (2-methoxy-4-methanesulfonyl-aminophenyl) -benzimidazole
    O - 2- (2-methoxy-4-methylthiomethylphenyl) -imidazo-L4,5-bj-pyridine;
    P is cyano-2- (4-methaisulfonyl-2-methoxyphenyl) benzimidazole;
    P is 5-acetylamino-2- (4-methanesulfonic 1-methoxyphenyl) benzimidazole;
    C is 5-amino-2- (4-methanesulfonyl-amino-2-methoxyphenyl) benzimidazole;
    T - 8- (2-methoxy-4-trifluoromethanesulfo-yloxyphenyl) -purine;
    Y - 2- (4-methanesulfonone-amino-2-methoxyphenyl) -imidazo-4,5-bj pyridine;
    F - 2- (4-methanesulfon1-shoxy-2-methoxyphenyl) -imidazo-t4,5-b pyridine;
    231
    X is 5-hydroxy-2- (4-methanesulfonyl-amino-2-methoxyphenyl) -benz-4 imidazole.
    The effects on blood pressure and a positively inotropic effect on anesthetized cats are determined.
    Cats anesthetized with pentobarbital in the form of sodium salt (40 mg / kg, intraperitoneally) were examined. Animals breathe spontaneously. Arterial blood pressure is measured in the abdominal aorta. To determine the positively inotropic effect, the pressure in the left ventricle of the heart is measured and the degree of contractility is determined using an analog differentiating device. The test compounds are initiated in Vena femoralis. Saline or polydiol 200 is used as a solvent. Each compound is given to at least three cats at a dose of 2 mg / kg {intravenously).
    The results of the experiment are given in .tabl. 1 Table 1

    24 Continued table. one

    Famous I
    II
    "2, 0 2.0
    +35 +87
    -5 / -6 -18 / -23
    2- (2-Methoxy-4-methylsulfinylphenyl) -1 H-imidazo-4, 5-bJ-pyridine, 8- (3,4-Dimethoxyphenyl) -purine.
    Elemental analysis data.
    2- (2 -Methoxy-4-meta-sulfonyl-aminophenyl) -6-oxyimidazo-4, pyridine.
    Calculated,%: C 50.29; H 4.22; N 16.76.
    Found,%: C 50.44; H 4.32; N 16.34.
    8- (2 -Methoxy-4-methylsulfinylmethylphenyl) -purine.
    Calculated,%: C 55.61; H 4.67; N 18,53.
    Found,%: C 55.39; H 4.67; N 18.21.
    5-aminocarbonyl-2- (2-methoxy-4-methanesulfonyloxyphenyl) benzimidazole.
    Calculated,%: C 53.18; H 4.18; N 11.63.
    Found,%: C 53.20; H 4.21; N 11.59.
    5 2- (2 -Methoxy-4-methylsulfonylmethyl-phenyl) -imidazo-4, ridine.
    Calculated,%: C 59.78; H 5.02; N 13.94,
    25
    Found,%: C 59.75; H 5.08; N 13.57.
    8- (2 -Methoxy-4-aminocarbonyl-phenyl) -purine.
    Calculated,%: C, 56.86; H 4.50; N 25, 85.
    Found,%: C 57.15; H 4.25; N 25.61.
    A comparison of the data on the activity of the proposed and known compounds indicates that not all of the proposed compounds have the best blood pressure lowering activity.
    However, the half-life of known compounds I, II is 5 and 4 min, respectively, whereas the half-life of the proposed compounds A – X is 15-75 min.
    In tab. Table 2 shows the toxicity of the compounds (determined 14 days after oral administration of each compound at a dose of 300 mg / kg to ten minutes).
    table 2
    Compound
    mg / kg
    JO
    300 (no mouse died)
    300 300
    权利要求:
    Claims (1)
    [1]
    Invention Formula
    five
     About 5 20
    25
    R6 - R, 30
    35
    26
    methyl, cyano-, methoxycarbonyl, aminocarbonyl, methyl-aminocarbonyl, nitro, amine-HO-, acetylamino, methoxycarbonylamino-, aminocarbonylamino-, methylaminocarbonylamino-, metal sulfonylamino-;
    Ry is hydrogen, methyl, methoxy; hydrogen or chlorine, methyl; alkinsulfonyloxy-, trifluoromethanesulfonyloxy-, alkanesulfonylamino-, N-alkyl-alkanesulfonylamino-, trifluoromethanesulfonylamino-, K-apkyl trifluoromethanesulfonyl-amino, alkylsulfenyl-meth-. Tyl, alkylsulfinylmethyl or alkylsulfonylmethyl, a carbonyl group substituted by a hydroxide, an alkoxylone, an amino, alkylamino or dialkylamino group, a sulfonyl group substituted by an amino, dialkylamino or morpholino group, each of the alkyl moieties of these groups containing 1 or 2 carbon of , nitrocyano, or alkylaminosulfonyl with 1-4 carbon atoms;
    ethyl, methoxy, dimethylamino;
    hydrogen or methoxy, or their acid addition salts, characterized in that the compound of the general formula
    R, Ra. A method for the preparation of derivatives with 40 dazole of the general formula
    where a and b together. with two carbon atoms between them means a group of the formula
    Nb
    (HAW-tfY
     V
    where R is hydrogen, fluorine, chlorine or
    bromine, methyl, hydroxyl, methoxy, trifluoromethyl, hydroxy
    AvyNH-X NH-Y
    45
    where A and B have the indicated meanings; one of the radicals X and Y is hydrogen, and the other is a group of the formula
    55
    where R ,, R and R, have the indicated meanings,
    obtained by the reaction of a compound of the general formula
    ,
    T
    ,
    27131655928
    where A and B have the indicated meanings, where R ,, R and K, have the indicated meanings with a compound of the general formula. ieHHH,
    rj subjected to cyclization at 50-200 C in
    nose
    Vg
    cyclized with ei-zuu
    the presence of a condensation agent followed by the allocation of the target product
    that in free form or in the form of an acid-additive salt.
    that in free form or in the form of an acid-additive salt.
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    同族专利:
    公开号 | 公开日
    PH20810A|1987-04-24|
    DK301383D0|1983-06-30|
    ES8500056A1|1984-10-01|
    FI832022L|1984-01-02|
    GB8317732D0|1983-08-03|
    PL242770A1|1986-10-21|
    ES8500241A1|1984-10-01|
    ES529174A0|1984-10-01|
    US4582837A|1986-04-15|
    CS254319B2|1988-01-15|
    US4696931A|1987-09-29|
    IL69111D0|1983-10-31|
    PL142880B1|1987-12-31|
    JPS5927875A|1984-02-14|
    GB2122995B|1986-02-12|
    ES523709A0|1984-10-01|
    EP0098448A2|1984-01-18|
    YU143283A|1986-06-30|
    ES529175A0|1984-10-01|
    DE3224512A1|1984-01-05|
    ES8500242A1|1984-10-01|
    AU1642883A|1984-01-05|
    KR840005432A|1984-11-12|
    PL144589B1|1988-06-30|
    DD210271A5|1984-06-06|
    GB2122995A|1984-01-25|
    PT76968A|1983-07-01|
    SU1179924A3|1985-09-15|
    NO832356L|1984-01-02|
    DK301383A|1984-01-02|
    ZA834777B|1985-03-27|
    HU192152B|1987-05-28|
    PT76968B|1986-04-09|
    GR78598B|1984-09-27|
    FI832022A0|1983-06-06|
    EP0098448A3|1985-04-03|
    NZ204766A|1986-09-10|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    DE19823224512|DE3224512A1|1982-07-01|1982-07-01|NEW IMIDAZOLE DERIVATIVES, THEIR PRODUCTION AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS|
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