Derivatives of n -[(1h-pyrazol-1-yl)aryl] - 1h - indole or 1h - indazole - 3 - carboxamide, their preparation and their use as p2y12 antagonists

摘要

N-[(1H-Pyrazol-1-yl)aryl]-1H-indole or 1H-indazole-3-carboxamide derivatives (I) are new. N-[(1H-Pyrazol-1-yl)aryl]-1H-indole or 1H-indazole-3-carboxamide derivatives of formula (I) in the form of a base or addition salt to an acid or base, are new. X : -CH or N; A : aromatic bivalent group comprising phenyl group of formula (a), pyrimidine, pyrazine or pyridazine; R1 : 1-4C alkyl or 1-4C alkoxy; R2 : Alk; R3 : OH or -NR7R8; R4 : H, halo, CN, phenyl, Alk, OAlk or -NR9R10; R5 : H, halo or Alk; R6 : H, halo, CN, -COOAlk or -CONH 2; either R7 : H or 1-4C alkyl; and R8 : 3-6C heterocycloalkyl (optionally substituted by 1-4C alkyl or -COOAlk), heteroaryl (optionally substituted by 1-4C alkyl), 3-7C cycloalkyl, 3-6C heterocycloalkyl (optionally substituted by 1-4C alkyl or -COOAlk), H, OH, OAlk or -SO 2Alk; or R7R8+N : optionally saturated, mono- or poly-cyclic, condensed or bridged 4-10C heterocycle ring comprising 1-3 other nitrogen atoms or another heteroatom comprising O or S, where the heterocycle is optionally substituted by 1-3 substituents of halo, OH, -OR11, oxo, -NR9R10, -NR12COR13, -NR12COOR13, -COR13, -COOR13, -CONR14R15, 3-7C cycloalkyl (optionally substituted with OH or 1-4C alkyl), 3-6C heterocycloalkyl (optionally substituted with 1 or 2 oxo groups), phenyl (optionally substituted by one or more substituents of halo, Alk or OAlk), pyridinyl or 1-4C alkyl (optionally substituted by one or more substituents of halo, OH, -OR11, -NR9R10, -NR12COR13, -COOR13, -CONR14R15, -SO 2Alk, 3-7C cycloalkyl, 3-6C heterocycloalkyl, phenyl (optionally substituted by one or more substituents of halo, Alk or OAlk) or heteroaryl (optionally substituted by 1-4C alkyl)); R9, R10 : H or 1-4C alkyl; R11 : Alk, 1-4C alkylene-OH or 1-4C alkylene-OAlk; R12 : H or 1-4C alkyl; R13 : 1-4C alkyl; either R14, R15 : H, 1-4C alkyl or 3-7C cycloalkyl; or R14, R15+N : heterocyclic group comprising azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl or piperazin-1-yl; and Alk : 1-4C alkyl (optionally substituted by F). Independent claims are included for: (1) a pyrazole compound of formula (II); and (2) the preparation of (I). Z : 1-4C alkyl. [Image] [Image] [Image] - ACTIVITY : Antianginal; Cardiant; Anticoagulant; Thrombolytic; Antiarteriosclerotic; Cerebroprotective; Vasotropic; Vulnerary; Cardiovascular-Gen.; Dermatological; Hemostatic; Immunosuppressive; Gynecological; Antiinflammatory; Nephrotropic; Gastrointestinal-Gen. - MECHANISM OF ACTION : Purinergic receptor P2Y G-protein coupled 12 (P2Y12) antagonist.