发明公开
- 专利标题: Cycloalkyl-substituted glutaramide antihypertensive agents
- 专利标题(中): 环烷基取代物戊二酰胺抗高血压
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申请号: EP89308740.3申请日: 1989-08-30
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公开(公告)号: EP0358398A1公开(公告)日: 1990-03-14
- 发明人: Danilewicz, John Christopher, Dr. , James, Keith, Dr. , Kobylecki, Ryszard Jurek, Dr.
- 申请人: Pfizer Limited , PFIZER INC.
- 申请人地址: Ramsgate Road Sandwich Kent CT13 9NJ GB
- 专利权人: Pfizer Limited,PFIZER INC.
- 当前专利权人: Pfizer Limited,PFIZER INC.
- 当前专利权人地址: Ramsgate Road Sandwich Kent CT13 9NJ GB
- 代理机构: Moore, James William, Dr.
- 优先权: GB8820844 19880905
- 主分类号: C07C237/20
- IPC分类号: C07C237/20 ; A61K31/21 ; C07D209/20 ; C07D231/56 ; C07C311/08 ; C07C235/82 ; C07F7/08 ; C07D213/82 ; C07D307/68 ; C07D207/16 ; C07D233/64
摘要:
Compounds of the formula:
Wherein A completes a 5 or 6 membered carbocyclic ring which may be saturated or monounsaturated; R 1 is H or (C 1 -C 4 )alkyl; R and R 4 are H, (C 1 -C 6 )alkyl, C 3 -C 7 cycloalkyl, benzyl, or an alternative biolabile ester-forming group;
Y is either a direct bond or an alkylene group of from 1 to 6 carbon atoms;
R 2 is H, aryl, heterocyclyl, R 6 CONR 5- , R 7 NR 5 CO-, R 7 NR 5 SO 2 - or R 8 SO 2 NR 5 -, with the proviso that Y is not a direct bond when R 2 is H, aryl or heterocyclyl;
wherein R 5 is H, (C 1 -C 6 )alkyl or aryl(C 1 -C 6 )alkyl; R 6 is (C 1 -C 6 )alkyl, aryl, aryl(C 1 -C 6 )alkyl, heterocyclyl, heterocyclyl(C 1 -C 6 )alkyl or a group of the formula R 9 R 10 R 11 C-wherein R 9 is H, OH, (C 1 -C 6 )alkoxy, (C 1 -C 6 )-alkyl, hydroxy(C 1 -C 6 )alkyl, aryl(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, heterocyclyl, heterocyclyl(C 1 -C 6 )alkyl, R 12 CONH-, R 12 SO 2 NH- or (R 13 ) 2 N-; R 10 and R 11 are H or (C 1 -C 6 )alkyl; or R 10 is H and R" is amino(C 1 -C 6 )-alkyl, imidazolylmethyl, aryl, aryl(C 1 -C 6 )alkyl, aryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkoxy, hydroxy(C 1 -C 6 )alkyl or methylthio(C I -C 6 )alkyl; or the two groups R 10 and R 11 form a 3 to 6 membered carbocyclic ring or a pyrrolidine or piperidine ring which may optionally be substituted by amino, (C 2 -C 4 )alkanoyl or aroyl; R 12 is (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, aryl, aryl(C 1 -C 6 )alkyl, heterocyclyl or heterocyclyl(C 1 -C 6 )alkyl; each R 13 is H, (C 1 -C 6 )alkyl, aryl(C 1 -C 6 )alkyl or the two groups R' 3 form a pyrrolidinyl, piperidino, morpholino, piperazinyl or N-(C 1 -C 4 )alkyl-piperazinyl group;
R 7 is (C 1 -C 6 )alkyl, aryl, aryl(C 1 -C 6 )alkyl, heterocyclyl, heterocyclyl(C 1 -C 6 )alkyl or a group of the formula R 10 R 11 R 14 C-wherein R 10 and R 11 are as previously defined and R 14 is (R' 3 ) 2 NCO-, R 12 0CH 2 - or R 15 OCO, wherein R 12 and R 13 are as previously defined and R 15 is (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl or aryl(C 1 -C 6 )alkyl; and
R 8 is (C 1 -C 6 )alkyl, aryl, aryl(C 1 -C 6 )alkyl, heterocyclyl or heterocyclyl(C 1 -C 6 )alkyl;
R 3 is a group of the formula:
wherein R 16 is H, halo, 4-OH, 4-(C 1 -C 6 alkoxy), 4-(C 3 -C 7 cycloalkoxy) 4-(C 2 -Cs alkenyloxy), 4-[(Ci-Cs alkoxy)carbonyloxy], 4-[(C 3 -C 7 cycloalkoxy)carbonyloxy], or 3-(C 1 -C 4 alkyl)S0 2 NH-; and R 20 is H, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 2 -C 6 alkanoyl or halo; or R 3 is a group of the formula:
wherein said groups may optionally be substituted in the fused benzene ring by C 1 -C 4 alkyl, C 1 -C 4 alkoxy, OH, halo or CF 3 ; are antihypertensive agents of utility in the treatment of hypertension, heart failure and renal insufficiency.
Wherein A completes a 5 or 6 membered carbocyclic ring which may be saturated or monounsaturated; R 1 is H or (C 1 -C 4 )alkyl; R and R 4 are H, (C 1 -C 6 )alkyl, C 3 -C 7 cycloalkyl, benzyl, or an alternative biolabile ester-forming group;
Y is either a direct bond or an alkylene group of from 1 to 6 carbon atoms;
R 2 is H, aryl, heterocyclyl, R 6 CONR 5- , R 7 NR 5 CO-, R 7 NR 5 SO 2 - or R 8 SO 2 NR 5 -, with the proviso that Y is not a direct bond when R 2 is H, aryl or heterocyclyl;
wherein R 5 is H, (C 1 -C 6 )alkyl or aryl(C 1 -C 6 )alkyl; R 6 is (C 1 -C 6 )alkyl, aryl, aryl(C 1 -C 6 )alkyl, heterocyclyl, heterocyclyl(C 1 -C 6 )alkyl or a group of the formula R 9 R 10 R 11 C-wherein R 9 is H, OH, (C 1 -C 6 )alkoxy, (C 1 -C 6 )-alkyl, hydroxy(C 1 -C 6 )alkyl, aryl(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, heterocyclyl, heterocyclyl(C 1 -C 6 )alkyl, R 12 CONH-, R 12 SO 2 NH- or (R 13 ) 2 N-; R 10 and R 11 are H or (C 1 -C 6 )alkyl; or R 10 is H and R" is amino(C 1 -C 6 )-alkyl, imidazolylmethyl, aryl, aryl(C 1 -C 6 )alkyl, aryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkoxy, hydroxy(C 1 -C 6 )alkyl or methylthio(C I -C 6 )alkyl; or the two groups R 10 and R 11 form a 3 to 6 membered carbocyclic ring or a pyrrolidine or piperidine ring which may optionally be substituted by amino, (C 2 -C 4 )alkanoyl or aroyl; R 12 is (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, aryl, aryl(C 1 -C 6 )alkyl, heterocyclyl or heterocyclyl(C 1 -C 6 )alkyl; each R 13 is H, (C 1 -C 6 )alkyl, aryl(C 1 -C 6 )alkyl or the two groups R' 3 form a pyrrolidinyl, piperidino, morpholino, piperazinyl or N-(C 1 -C 4 )alkyl-piperazinyl group;
R 7 is (C 1 -C 6 )alkyl, aryl, aryl(C 1 -C 6 )alkyl, heterocyclyl, heterocyclyl(C 1 -C 6 )alkyl or a group of the formula R 10 R 11 R 14 C-wherein R 10 and R 11 are as previously defined and R 14 is (R' 3 ) 2 NCO-, R 12 0CH 2 - or R 15 OCO, wherein R 12 and R 13 are as previously defined and R 15 is (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl or aryl(C 1 -C 6 )alkyl; and
R 8 is (C 1 -C 6 )alkyl, aryl, aryl(C 1 -C 6 )alkyl, heterocyclyl or heterocyclyl(C 1 -C 6 )alkyl;
R 3 is a group of the formula:
wherein R 16 is H, halo, 4-OH, 4-(C 1 -C 6 alkoxy), 4-(C 3 -C 7 cycloalkoxy) 4-(C 2 -Cs alkenyloxy), 4-[(Ci-Cs alkoxy)carbonyloxy], 4-[(C 3 -C 7 cycloalkoxy)carbonyloxy], or 3-(C 1 -C 4 alkyl)S0 2 NH-; and R 20 is H, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 2 -C 6 alkanoyl or halo; or R 3 is a group of the formula:
wherein said groups may optionally be substituted in the fused benzene ring by C 1 -C 4 alkyl, C 1 -C 4 alkoxy, OH, halo or CF 3 ; are antihypertensive agents of utility in the treatment of hypertension, heart failure and renal insufficiency.
公开/授权文献
- EP0358398B1 Cycloalkyl-substituted glutaramide antihypertensive agents 公开/授权日:1993-03-10
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