公开(公告)号：EP0309423A3

公开(公告)日：1989-11-29

申请号：EP88830375.7

申请日：1988-09-19

申请人： BOEHRINGER INGELHEIM ITALIA S.p.A.

发明人： Turconi, Marco ,  Donetti, Arturo ,  Micheletti, Rosamaria ,  Uberti, Annamaria ,  Nicola, Massimo ,  Giachetti, Antonio ,  Montagna, Ernesto

IPC分类号： C07D451/12 ,  C07D453/02 ,  C07D401/12 ,  C07D451/14 ,  C07D403/12 ,  C07D453/06 ,  C07D451/04 ,  A61K31/46 ,  A61K31/445 ,  A61K31/435

CPC分类号： C07D401/12 ,  C07D451/12 ,  C07D451/14 ,  C07D453/02 ,  C07D453/06 ,  C07D487/08

摘要： New pharmacologically active benzimidazoline-2-oxo-1-carboxylic acid derivatives which are 5-HT receptor antagonists useful as antiemetic agents and as gastric prokinetic agents of the following formula:
wherein R represents a hydrogen atom, C₁₋₆ alkyl, C₁₋₆ alkenyl or C₁₋₆ alkynil; R₁ and R₂ may be at the same time or not a hydrogen atom, halogen, trifluoromethyl, C₁₋₆ alkyl, C₁₋₆ alkoxy, C₁₋₆ alkylthio, C₁₋₆ acyl, carboxyl, C₁₋₆ alkoxycarbonyl, hydroxy, nitro, amino optio­nally C₁₋₄ alkyl N-mono or di-substituted, C₁₋₆ acylamino, C₁₋₆ alkoxy­carbonylamino, carbamoyl optionally C₁₋₄ alkyl N-mono or di-substitu­ted, cyano, C₁₋₆alkylsulphinyl, C₁₋₆ alkylsulphonyl, amino sulphonyl optionally C₁₋₄ alkyl N-mono or di-substituted, C₁₋₄ alkyl N-mono or di-substituted aminosulphonylamino, aminosulphonylamino; Y is oxygen or is N - R₃ in which R₃ is a hydrogen, a C₁₋₆ alkyl or optionally substituted by one or more C₁₋₆ alkoxy benzyl; A is a group selected from: wherein p is 0, 1; r is 0, 1, 2, 3; R₄ is hydrogen atom or a C₁₋₄ alkyl; R₅ is a hydrogen atom, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl C₁₋₄ alkyl,substituted phenyl C₁₋₄ alkyl or R₅ is a group of formula
wherein R₆ is hydrogen atom, C₁₋₄ alkyl or an amino group and R₇ is hydrogen atom or C₁₋₆ alkyl, tautomers thereof and acid addition salts of the aforesaid compounds. The processes for the preparation of the compounds of formula (I) as well as pharmaceutical compositions containing them are also described.

公开(公告)号：EP0309423B1

公开(公告)日：1994-06-15

申请号：EP88830375.7

申请日：1988-09-19

申请人： BOEHRINGER INGELHEIM ITALIA S.p.A.

发明人： Turconi, Marco ,  Donetti, Arturo ,  Micheletti, Rosamaria ,  Uberti, Annamaria ,  Nicola, Massimo ,  Giachetti, Antonio ,  Montagna, Ernesto

IPC分类号： C07D451/12 ,  C07D453/02 ,  C07D401/12 ,  C07D451/14 ,  C07D403/12 ,  C07D453/06 ,  C07D451/04 ,  A61K31/46 ,  A61K31/445 ,  A61K31/435

CPC分类号： C07D401/12 ,  C07D451/12 ,  C07D451/14 ,  C07D453/02 ,  C07D453/06 ,  C07D487/08

公开(公告)号：EP0309423A2

公开(公告)日：1989-03-29

申请号：EP88830375.7

申请日：1988-09-19

申请人： BOEHRINGER INGELHEIM ITALIA S.p.A.

发明人： Turconi, Marco ,  Donetti, Arturo ,  Micheletti, Rosamaria ,  Uberti, Annamaria ,  Nicola, Massimo ,  Giachetti, Antonio ,  Montagna, Ernesto

IPC分类号： C07D451/12 ,  C07D453/02 ,  C07D401/12 ,  C07D451/14 ,  C07D403/12 ,  C07D453/06 ,  C07D451/04 ,  A61K31/46 ,  A61K31/445 ,  A61K31/435

CPC分类号： C07D401/12 ,  C07D451/12 ,  C07D451/14 ,  C07D453/02 ,  C07D453/06 ,  C07D487/08

摘要： New pharmacologically active benzimidazoline-2-oxo-1-carboxylic acid derivatives which are 5-HT receptor antagonists useful as antiemetic agents and as gastric prokinetic agents of the following formula:
wherein R represents a hydrogen atom, C₁₋₆ alkyl, C₁₋₆ alkenyl or C₁₋₆ alkynil; R₁ and R₂ may be at the same time or not a hydrogen atom, halogen, trifluoromethyl, C₁₋₆ alkyl, C₁₋₆ alkoxy, C₁₋₆ alkylthio, C₁₋₆ acyl, carboxyl, C₁₋₆ alkoxycarbonyl, hydroxy, nitro, amino optio­nally C₁₋₄ alkyl N-mono or di-substituted, C₁₋₆ acylamino, C₁₋₆ alkoxy­carbonylamino, carbamoyl optionally C₁₋₄ alkyl N-mono or di-substitu­ted, cyano, C₁₋₆alkylsulphinyl, C₁₋₆ alkylsulphonyl, amino sulphonyl optionally C₁₋₄ alkyl N-mono or di-substituted, C₁₋₄ alkyl N-mono or di-substituted aminosulphonylamino, aminosulphonylamino; Y is oxygen or is N - R₃ in which R₃ is a hydrogen, a C₁₋₆ alkyl or optionally substituted by one or more C₁₋₆ alkoxy benzyl; A is a group selected from:
wherein p is 0, 1; r is 0, 1, 2, 3; R₄ is hydrogen atom or a C₁₋₄ alkyl; R₅ is a hydrogen atom, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl C₁₋₄ alkyl,substituted phenyl C₁₋₄ alkyl or R₅ is a group of formula
wherein R₆ is hydrogen atom, C₁₋₄ alkyl or an amino group and R₇ is hydrogen atom or C₁₋₆ alkyl, tautomers thereof and acid addition salts of the aforesaid compounds.
The processes for the preparation of the compounds of formula (I) as well as pharmaceutical compositions containing them are also described.

摘要翻译： 新的药理活性苯并咪唑啉-2-氧代-1-羧酸衍生物，其为可用作止吐剂的5-HT受体拮抗剂和作为下式的胃促动力剂：其中R表示氢原子，C 1-6烷基， C 1-6烯基或C 1-6炔烃; R 1和R 2可以同时或不是氢原子，卤素，三氟甲基，C 1-6烷基，C 1-6烷氧基，C 1-6烷硫基，C 1-6酰基，羧基，C 1-6烷氧基羰基，羟基，硝基， 氨基任选C 1-4烷基N-单或二取代的C 1-6酰基氨基，C 1-6烷氧基羰基氨基，氨基甲酰基任选C 1-4烷基N-单或二取代，氰基，C 1-6烷基亚磺酰基，C 1-6烷基磺酰基，氨基 磺酰基任选C 1-4烷基N-单或二取代的C 1-4烷基N-单或二取代氨基磺酰基氨基，氨基磺酰基氨基; Y是氧，或者是其中R 3是氢，C 1-6烷基或任选地被一个或多个C 1-6烷氧基苄基取代的N-R 3; A是选自以下的基团：，其中p是0,1; r为0,1,2,3; R4是氢原子或C1-4烷基; R5是氢原子，C1-6烷基，C3-8环烷基，C3-8环烷基C1-4烷基，取代苯基C1-4烷基或R5是式CHEM的基团，其中R6是氢原子，C1-4 烷基或氨基，R 7为氢原子或C 1-6烷基，其互变异构体和上述化合物的酸加成盐。 还描述了制备式（I）化合物的方法以及含有它们的药物组合物。