发明公开
- 专利标题: Spiro-subsituted glutaramide diuretic agents
- 专利标题(中): 螺旋替代物戊二酰胺
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申请号: EP87310784.1申请日: 1987-12-08
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公开(公告)号: EP0274234A2公开(公告)日: 1988-07-13
- 发明人: Barnish, Ian Thompson, Dr. , James, Keith, Dr. , Terrett, Nicholas Kenneth, Dr. , Danilewicz, John Christopher, Dr. , Samuels, Gillian Mary Ryder, Dr. , Wythes, Martin James, Dr.
- 申请人: Pfizer Limited
- 申请人地址: Ramsgate Road Sandwich Kent CT13 9NJ GB
- 专利权人: Pfizer Limited
- 当前专利权人: Pfizer Limited
- 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: GB8629663 19861211; GB8715722 19870703
- 主分类号: C07C233/57
- IPC分类号: C07C233/57 ; C07D207/327 ; C07D295/14 ; A61K31/16 ; A61K31/445 ; A61K31/535 ; A61K31/40 ; A61K31/495 ; C07C311/01 ; C07C311/15
摘要:
Compounds of the formula
wherein A completes a 4 or 7 membered carbocyclic ring which may be saturated or mono-unsaturated and which may optionally be fused to a further saturated or unsaturated 5 or 6 membered carbocyclic ring; B is (CH 2 ) m wherein m is an integer of from 1 to 3; each of R and R 4 is independently H, C 1 -C 6 alkyl, benzyl or an alternative biolabile ester-forming group; R 1 is H or C 1 -C 4 alkyl; R 2 and R 3 are each independently H, OH, C 1 -C 4 alkyl or C 1 -C 4 alkoxy; and R 5 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, aryl(C 2 -C 6 alkynyl), C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkenyl, C 1 -C 6 alkoxy, -NR 6 R 7 , -NR 8 COR 9 , -NR 8 SO 2 R 9 or a saturated heterocyclic group; or C 1 -C 6 alkyl substituted by one or more substituents chosen from halo, hydroxy, C 1 -C 6 alkoxy, C 2 -C 6 hydroxyalkoxy, C 1 -C 6 alkoxy(C 1 -C 6 alkoxy), C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkenyl, aryl, aryloxy, arlyoxy(C I -C 4 alkoxy), heterocyclyl, heterocyclyloxy, -NR 6 R 7 , -NR8COR9, -NR 8 SO 2 R 9 , -CONR 6 R 7 , -SH, -S(O) p R 10 , -COR 11 or -CO 2 R 12 ; wherein R 6 and R 7 are each independently H, C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl (optionally substituted by hydroxy or C 1 -C 4 alkoxy), aryl, aryl(C 1 -C 4 alkyl), CrCs alkoxyalkyl, or heterocyclyl; or the two groups R 6 and R 7 are taken together with the nitrogen to which they are attached to form a pyrrolidinyl, piperidino, morpholino, piperazinyl or N-(C 1 -C 4 alkyl)-piperazinyl group; R 8 is H or C 1 -C 4 alkyl; R 9 is C 1 -C 4 alkyl, CF 3 , aryl, aryl(C I -C 4 alkyl), aryl(C 1 -C 4 alkoxy), heterocycyl, C 1 -C 4 alkoxy or NR 6 R 7 wherein R 6 and R 7 are as previously defined; R 10 is C 1 -C 4 alkyl, aryl, heterocyclyl or NR 6 R 7 wherein R 6 and R 7 are as previously defined; R 11 is C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, aryl or heterocyclyl; R 12 is H or Ci-C 4 alkyl; and p is 0, 1 or 2; or a pharmaceutically acceptable salts thereof or bioprecursor therefor are diuretic agents having utility in the treatment of hypertension, heart failure, renal insufficiency and in other disorders.
wherein A completes a 4 or 7 membered carbocyclic ring which may be saturated or mono-unsaturated and which may optionally be fused to a further saturated or unsaturated 5 or 6 membered carbocyclic ring; B is (CH 2 ) m wherein m is an integer of from 1 to 3; each of R and R 4 is independently H, C 1 -C 6 alkyl, benzyl or an alternative biolabile ester-forming group; R 1 is H or C 1 -C 4 alkyl; R 2 and R 3 are each independently H, OH, C 1 -C 4 alkyl or C 1 -C 4 alkoxy; and R 5 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, aryl(C 2 -C 6 alkynyl), C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkenyl, C 1 -C 6 alkoxy, -NR 6 R 7 , -NR 8 COR 9 , -NR 8 SO 2 R 9 or a saturated heterocyclic group; or C 1 -C 6 alkyl substituted by one or more substituents chosen from halo, hydroxy, C 1 -C 6 alkoxy, C 2 -C 6 hydroxyalkoxy, C 1 -C 6 alkoxy(C 1 -C 6 alkoxy), C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkenyl, aryl, aryloxy, arlyoxy(C I -C 4 alkoxy), heterocyclyl, heterocyclyloxy, -NR 6 R 7 , -NR8COR9, -NR 8 SO 2 R 9 , -CONR 6 R 7 , -SH, -S(O) p R 10 , -COR 11 or -CO 2 R 12 ; wherein R 6 and R 7 are each independently H, C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl (optionally substituted by hydroxy or C 1 -C 4 alkoxy), aryl, aryl(C 1 -C 4 alkyl), CrCs alkoxyalkyl, or heterocyclyl; or the two groups R 6 and R 7 are taken together with the nitrogen to which they are attached to form a pyrrolidinyl, piperidino, morpholino, piperazinyl or N-(C 1 -C 4 alkyl)-piperazinyl group; R 8 is H or C 1 -C 4 alkyl; R 9 is C 1 -C 4 alkyl, CF 3 , aryl, aryl(C I -C 4 alkyl), aryl(C 1 -C 4 alkoxy), heterocycyl, C 1 -C 4 alkoxy or NR 6 R 7 wherein R 6 and R 7 are as previously defined; R 10 is C 1 -C 4 alkyl, aryl, heterocyclyl or NR 6 R 7 wherein R 6 and R 7 are as previously defined; R 11 is C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, aryl or heterocyclyl; R 12 is H or Ci-C 4 alkyl; and p is 0, 1 or 2; or a pharmaceutically acceptable salts thereof or bioprecursor therefor are diuretic agents having utility in the treatment of hypertension, heart failure, renal insufficiency and in other disorders.
公开/授权文献
- EP0274234B1 Spiro-subsituted glutaramide diuretic agents 公开/授权日:1991-09-11
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