4,5,6,7-Tetrahydro-1H-imidazo 4,5-c pyridine-6-carboxylic acid amide derivatives as angiotensine II antagonistes
申请人:KUREHA KAGAKU KOGYO KABUSHIKI KAISHA
公开号:EP0589665A2
公开(公告)日:1994-03-30
A compound of formula (I):
or a pharmaceutically acceptable salt thereof; wherein
R¹ represents
hydrogen,
halogen,
C₁-C₆ alkyl,
C₃-C₆ alkenyl,
C₃-C₆ alkynyl,
R²⁰(CH₂)n- wherein R²⁰ represents C₃-C₈ cycloalkyl, naphthyl, phenyl, or phenyl substituted with one to five of C₁-C₄ alkyl, halogen atom, trifluoromethyl, hydroxy, C₁-C₄ alkoxy, C₁-C₃ acyloxy, amino, N-mono-C₁-C₄ alkylamino, N-di-C₁-C₄ alkylamino, C₁-C₄ thioalkyl, C₁-C₃ alkylsulfonyl, nitro, and -NHCOR²¹ wherein R²¹ represents C₁-C₃ alkyl, phenyl, C₁-C₃ alkylphenyl, aminophenyl, or C₁-C₄ alkylaminophenyl, and n is an integer of 1 to 6,
R²⁰-C(O)- wherein R²⁰ is as defined above, or
R²⁰-CH(OH)- wherein R²⁰ is as defined above;
R² represents carbamoyl, mono- or di-C₁-C₆ alkylcarbamoyl, or 4- to 6-membered heterocyclic carbamoyl;
R represents amino, carboxy, (1H-tetrazol-5-yl)phenyl, carboxyphenyl, carboxybenzamido, (1H-tetrazol-5-yl)benzamido, carboxyphenylcarbamoyl, or (1H-tetrazol-5-yl)-phenylcarbamoyl;
R³ represents -CH₂(phenyl), -CH(phenyl)₂, -CH(phenyl)CH₃, -CH(phenyl) (cyclohexyl), -CH₂CH₂(phenyl), -CH₂(C₁-C₆ alkoxyphenyl), or -CH₂(hydroxyphenyl); and
R⁴, R⁷, and R⁸ each independently represents hydrogen or C₁-C₆ alkyl, is an angiotensin II antagonist.
式 (I) 的化合物:
或其药学上可接受的盐;其中
R¹ 代表
氢
卤素
C₁-C₆ 烷基
C₃-C₆ 烯基、
C₃-C₆ 烷基、
R²⁰(CH₂)n- 其中 R²⁰ 代表 C₃-C₈ 环烷基、萘基、苯基或被 1 至 5 个 C₁-C₄ 烷基取代的苯基、卤素原子、三氟甲基、羟基、C₁-C₄ 烷氧基、C₁-C₃酰氧基、氨基、N-单-C₁-C₄ 烷基氨基、N-二-C₁-C₄烷基氨基、C₁-C₄硫烷基、C₁-C₃烷基磺酰基、硝基和-NHCOR²¹,其中 R²¹ 代表 C₁-C₃烷基、苯基、C₁-C₃ 烷基苯基、氨基苯基或 C₁-C₄ 烷氨基苯基,且 n 为 1-6 的整数、
R²⁰-C(O)- 其中 R²⁰ 如上定义,或
R²⁰-CH(OH)- 其中 R²⁰ 如上定义;
R² 代表氨基甲酰基、单-或双-C₁-C₆ 烷基氨基甲酰基或 4-6 元杂环氨基甲酰基;
R 代表氨基、羧基、(1H-四唑-5-基)苯基、羧基苯基、羧基苯甲酰胺基、(1H-四唑-5-基)苯甲酰胺基、羧基苯基氨基甲酰基或 (1H-四唑-5-基)-苯基氨基甲酰基;
R³ 代表-CH₂(苯基)、-CH(苯基)₂、-CH(苯基)CH₃、-CH(苯基)(环己基)、-CH₂CH₂(苯基)、-CH₂(C₁-C₆烷氧基苯基)或-CH₂(羟基苯基);以及
R⁴、R⁷ 和 R⁸ 各自独立地代表氢或 C₁-C₆ 烷基,是血管紧张素 II 拮抗剂。