公开(公告)号：EP0343911A3

公开(公告)日：1991-01-16

申请号：EP89305180.5

申请日：1989-05-23

申请人： Pfizer Limited ,  PFIZER INC.

发明人： James, Keith, Dr. ,  Danilewicz, John Christopher, Dr.

IPC分类号： C07C103/737 ,  A61K31/215 ,  C07K5/06 ,  C07D213/82 ,  A61K31/455 ,  C07D295/18 ,  A61K31/40 ,  C07D207/14

CPC分类号： C07D213/82 ,  A61K38/00 ,  C07C233/63 ,  C07C235/40 ,  C07C237/24 ,  C07C271/22 ,  C07C311/06 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07D277/06 ,  C07D295/185 ,  C07K5/0207 ,  C07K5/06086

摘要： Compounds having the formula:
wherein A completes a 4 to 7 membered carbocyclic ring which may be saturated or mono-unsaturated and which may optionally be fused to a further carbocyclic ring; B is (CH 2 ) m wherein m is 1 to 3; R and R 4 are H, C 1 -C 6 alkyl, benzyl or biolabile ester-forming groups; R 1 is H or C 1 -C 4 alkyl; R 2 and R 3 are each H, OH, C 1 -C 6 alkyl or C 1 -C 6 alkoxy, or are linked together and are (CH 2 ) r wherein r is 1 to 4; Y is an optional alkylene group of from 1 to 6 carbon atoms which may be straight or branched-chain;
and R 5 is R 6 CONR 9- , R 6 SO 2 NR 9 -, R 6 CO 2 -, R 6 CO-, R 6 SOq-, R 7 NR 9 CO-, R 7 NR 9 S0 2 - or R 7 0CO-; wherein R 6 is a group of the formula R 8 (R 1O R 11 C-CONR 9 ) n R 1O R 11 C-; R 7 is a group of the formula R 10 R 11 R 12 C- and R 9 is H, C 1 -C 6 alkyl, aryl, C 3 -C 7 cycloalkyl, heterocyclyl, aryl(C 1 -C 6 alkyl) or heterocyclyl(C 1 -C 6 alkyl); wherein R 8 is R 9 CONR 9 -, R 9 SO 2 NR 9 -, R 13 R 14 -N-(CH 2 ) p -, or R 9 0-, R 10 and R 11 are H or C 1 -C 6 alkyl; or R 10 is H and R 11 is C 1 -C 6 alkyl which is substituted by OH, SH, SCH 3 , NH 2 , aryl(C 1 -C 6 alkyl)OCONH-, NH 2 CO-, C0 2 H, guanidino, aryl, or heterocyclyl; or the two groups R 10 and R 11 are joined to form a five or 6 membered carbocyclic ring which may be saturated, mono-unsaturated, optionally substituted by C 1 -C 4 alkyl or fused to a further carbocylic ring; or R 8 and R 11 are linked to form a 2-(N-COR 9- 4-aminopyrrolidinyl) group; R 12 is R 13 R 14 NCO-, R 9 0CO-, R 9 0CH 2 - or heterocyclyl, R 13 and R 14 are H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, aryl, aryl(C 1 -C 6 alkyl), C 2 -C s alkoxyalkyl, amino (C 1 -C 6 alkyl), heterocyclyl or heterocyclyl(C 1 -C 6 alkyl); or the two groups R 13 and R 14 form a pyrrolidinyl, piperidino, morpholino, piperazinyl, N-(C 1 -C 4 alkyl) piperazinyl, pyrrolyl, imidazolyl, pyrazolyl or triazolyl group; n is 0 or 1; p is 0 or 1 to 6; and q is 0, 1 or 2; and pharmaceutically acceptable salts thereof and bioprecursors therefor, are diuretic agents of value in the treatment of hypertension, heart failure and renal insufficiency.

摘要翻译： 具有下式的化合物：其中A完成4至7元碳环，其可以是饱和或单不饱和的，并且可任选地与另外的碳环稠合; B是（CH 2）m，其中m是1至3; R和R 4是H，C 1 -C 6烷基，苄基或生物不稳定酯形成基团; R 1是H或C 1 -C 4烷基; R 2和R 3各自为H，OH，C 1 -C 6烷基或C 1 -C 6烷氧基，或连接在一起并且为（CH 2）r，其中r为1至4; Y是可以是直链或支链的1-6个碳原子的任选的亚烷基; R 5是R 6 CONR 9 - ，R 6 SO 2 NR 9 - ，R 6 CO 2 - ，R 6 CO-，R 6 SOQ-，R 7 NR 9，CO - ，R 7 NR 9 SO 2 - 或R 7 OCO-; 其中R 6是式R 8的基团（R 1）R 1 C-CONR 9）n R 1 R 1 > C-; R 7是式R 1，R 1，R 2，C和R 9是H，C 1 -C 6烷基，芳基，C 3 -C 6环烷基， C7环烷基，杂环基，芳基（C1-C6烷基）或杂环基（C1-C6烷基）; 其中R 8是R 9 CONR 9 - ，R 9 SO 2 NR 9 - ，R 1，R 3，N - （CH 2）p - 或R O，R 1，O和R 1是H或C 1 -C 6烷基; 或R 1为H且R 1为被OH，SH，SCH 3，NH 2，芳基（C 1 -C 6烷基）OCONH-，NH 2 CO-，CO 2 H， 胍基，芳基或杂环基; 或两个基团R 1和R 1连接形成五元或六元碳环，其可以是饱和的，单不饱和的，任选地被C 1 -C 4烷基取代或稠合到 进一步的碳环; 或R 8和R 1'连接形成2-（N-COR 9-14-氨基吡咯烷基）基团; R 1是R 1，R 3，R 3，NCO-，R 9 OCO-，R 9 OCH 2 - 或杂环基，R 1和R 3 C 1 -C 6烷基，C 1 -C 6烷基，C 2 -C 6烷氧基烷基，氨基（C 1 -C 6烷基），杂环基或杂环基（C 1 -C 6烷基） ; 或两个基团R 1，R 3和R 4形成吡咯烷基，哌啶子基，吗啉代，哌嗪基，N-（C 1 -C 4烷基）哌嗪基，吡咯基，咪唑基，吡唑基或三唑基; n为0或1; p为0或1至6; q为0,1或2; 及其药学上可接受的盐及其生物前体是治疗高血压，心力衰竭和肾功能不全的利尿剂。

公开(公告)号：EP0343911A2

公开(公告)日：1989-11-29

申请号：EP89305180.5

申请日：1989-05-23

申请人： Pfizer Limited ,  PFIZER INC.

发明人： James, Keith, Dr. ,  Danilewicz, John Christopher, Dr.

IPC分类号： C07C103/737 ,  A61K31/215 ,  C07K5/06 ,  C07D213/82 ,  A61K31/455 ,  C07D295/18 ,  A61K31/40 ,  C07D207/14

CPC分类号： C07D213/82 ,  A61K38/00 ,  C07C233/63 ,  C07C235/40 ,  C07C237/24 ,  C07C271/22 ,  C07C311/06 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07D277/06 ,  C07D295/185 ,  C07K5/0207 ,  C07K5/06086

摘要： Compounds having the formula:
wherein A completes a 4 to 7 membered carbocyclic ring which may be saturated or mono-unsaturated and which may optionally be fused to a further carbocyclic ring; B is (CH 2 ) m wherein m is 1 to 3; R and R 4 are H, C 1 -C 6 alkyl, benzyl or biolabile ester-forming groups; R 1 is H or C 1 -C 4 alkyl; R 2 and R 3 are each H, OH, C 1 -C 6 alkyl or C 1 -C 6 alkoxy, or are linked together and are (CH 2 ) r wherein r is 1 to 4; Y is an optional alkylene group of from 1 to 6 carbon atoms which may be straight or branched-chain;

and R 5 is R 6 CONR 9- , R 6 SO 2 NR 9 -, R 6 CO 2 -, R 6 CO-, R 6 SOq-, R 7 NR 9 CO-, R 7 NR 9 S0 2 - or R 7 0CO-; wherein R 6 is a group of the formula R 8 (R 1O R 11 C-CONR 9 ) n R 1O R 11 C-; R 7 is a group of the formula R 10 R 11 R 12 C- and R 9 is H, C 1 -C 6 alkyl, aryl, C 3 -C 7 cycloalkyl, heterocyclyl, aryl(C 1 -C 6 alkyl) or heterocyclyl(C 1 -C 6 alkyl); wherein R 8 is R 9 CONR 9 -, R 9 SO 2 NR 9 -, R 13 R 14 -N-(CH 2 ) p -, or R 9 0-, R 10 and R 11 are H or C 1 -C 6 alkyl; or R 10 is H and R 11 is C 1 -C 6 alkyl which is substituted by OH, SH, SCH 3 , NH 2 , aryl(C 1 -C 6 alkyl)OCONH-, NH 2 CO-, C0 2 H, guanidino, aryl, or heterocyclyl; or the two groups R 10 and R 11 are joined to form a five or 6 membered carbocyclic ring which may be saturated, mono-unsaturated, optionally substituted by C 1 -C 4 alkyl or fused to a further carbocylic ring; or R 8 and R 11 are linked to form a 2-(N-COR 9- 4-aminopyrrolidinyl) group; R 12 is R 13 R 14 NCO-, R 9 0CO-, R 9 0CH 2 - or heterocyclyl, R 13 and R 14 are H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, aryl, aryl(C 1 -C 6 alkyl), C 2 -C s alkoxyalkyl, amino (C 1 -C 6 alkyl), heterocyclyl or heterocyclyl(C 1 -C 6 alkyl); or the two groups R 13 and R 14 form a pyrrolidinyl, piperidino, morpholino, piperazinyl, N-(C 1 -C 4 alkyl) piperazinyl, pyrrolyl, imidazolyl, pyrazolyl or triazolyl group; n is 0 or 1; p is 0 or 1 to 6; and q is 0, 1 or 2; and pharmaceutically acceptable salts thereof and bioprecursors therefor, are diuretic agents of value in the treatment of hypertension, heart failure and renal insufficiency.

摘要翻译： 具有下式的化合物：其中A完成4至7元碳环，其可以是饱和或单不饱和的，并且可任选地与另外的碳环稠合; B是（CH 2）m，其中m是1至3; R和R 4是H，C 1 -C 6烷基，苄基或生物不稳定酯形成基团; R 1是H或C 1 -C 4烷基; R 2和R 3各自为H，OH，C 1 -C 6烷基或C 1 -C 6烷氧基，或连接在一起并且为（CH 2）r，其中r为1至4; Y是可以是直链或支链的1-6个碳原子的任选的亚烷基; R 5是R 6 CONR 9 - ，R 6 SO 2 NR 9 - ，R 6 CO 2 - ，R 6 CO-，R 6 SOQ-，R 7 NR 9，CO - ，R 7 NR 9 SO 2 - 或R 7 OCO-; 其中R 6是式R 8的基团（R 1）R 1 C-CONR 9）n R 1 R 1 > C-; R 7是式R 1，R 1，R 2，C和R 9是H，C 1 -C 6烷基，芳基，C 3 -C 6环烷基， C7环烷基，杂环基，芳基（C1-C6烷基）或杂环基（C1-C6烷基）; 其中R 8是R 9 CONR 9 - ，R 9 SO 2 NR 9 - ，R 1，R 3，N - （CH 2）p - 或R O，R 1，O和R 1是H或C 1 -C 6烷基; 或R 1为H且R 1为被OH，SH，SCH 3，NH 2，芳基（C 1 -C 6烷基）OCONH-，NH 2 CO-，CO 2 H， 胍基，芳基或杂环基; 或两个基团R 1和R 1连接形成五元或六元碳环，其可以是饱和的，单不饱和的，任选地被C 1 -C 4烷基取代或稠合到 进一步的碳环; 或R 8和R 1'连接形成2-（N-COR 9-14-氨基吡咯烷基）基团; R 1是R 1，R 3，R 3，NCO-，R 9 OCO-，R 9 OCH 2 - 或杂环基，R 1和R 3 C 1 -C 6烷基，C 1 -C 6烷基，C 2 -C 6烷氧基烷基，氨基（C 1 -C 6烷基），杂环基或杂环基（C 1 -C 6烷基） ; 或两个基团R 1，R 3和R 4形成吡咯烷基，哌啶子基，吗啉代，哌嗪基，N-（C 1 -C 4烷基）哌嗪基，吡咯基，咪唑基，吡唑基或三唑基; n为0或1; p为0或1至6; q为0,1或2; 及其药学上可接受的盐及其生物前体是治疗高血压，心力衰竭和肾功能不全的利尿剂。

公开(公告)号：EP0358398B1

公开(公告)日：1993-03-10

申请号：EP89308740.3

申请日：1989-08-30

申请人： Pfizer Limited ,  PFIZER INC.

发明人： Danilewicz, John Christopher, Dr. ,  James, Keith, Dr. ,  Kobylecki, Ryszard Jurek, Dr.

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

CPC分类号： C07F7/0818 ,  C07C233/65 ,  C07C235/82 ,  C07C237/24 ,  C07C271/22 ,  C07C271/24 ,  C07C311/06 ,  C07C311/08 ,  C07C311/19 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2601/18 ,  C07D207/08 ,  C07D207/16 ,  C07D209/18 ,  C07D209/20 ,  C07D213/82 ,  C07D231/12 ,  C07D231/56 ,  C07D233/56 ,  C07D233/64 ,  C07D249/08 ,  C07D307/68 ,  C07D317/40

公开(公告)号：EP0274234A2

公开(公告)日：1988-07-13

申请号：EP87310784.1

申请日：1987-12-08

申请人： Pfizer Limited

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.

IPC分类号： C07C233/57 ,  C07D207/327 ,  C07D295/14 ,  A61K31/16 ,  A61K31/445 ,  A61K31/535 ,  A61K31/40 ,  A61K31/495 ,  C07C311/01 ,  C07C311/15

CPC分类号： C07D241/12 ,  C07D209/46 ,  C07D213/56 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D261/10 ,  C07D277/36 ,  C07D277/46 ,  C07D295/185 ,  C07D307/16 ,  C07D307/68 ,  C07D321/08 ,  C07D333/34

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.

摘要翻译： 其中A完成4或7元碳环，其可以是饱和或单不饱和的，并且可以任选地与另外的饱和或不饱和的5或6元碳环稠合; B是（CH 2）m，其中m是1至3的整数; R和R 4中的每一个独立地是H，C 1 -C 6烷基，苄基或替代的生物不稳定酯形成基团; R 1是H或C 1 -C 4烷基; R 2和R 3各自独立地为H，OH，C 1 -C 4烷基或C 1 -C 4烷氧基; 并且R 5是C 1 -C 6烷基，C 2 -C 6烯基，C 2 -C 6炔基，芳基（C 2 -C 6炔基），C 3 -C 7环烷基，C 3 -C 7环烯基，C 1 -C 6烷氧基，-NR 6 R -NR 8 COR 9，-NR 8 SO 2 R 9或饱和杂环基; 或被一个或多个选自卤素，羟基，C 1 -C 6烷氧基，C 2 -C 6羟基烷氧基，C 1 -C 6烷氧基（C 1 -C 6烷氧基），C 3 -C 7环烷基，C 3 -C 7环烯基，芳基， 芳氧基，芳氧基（C 1 -C 4烷氧基），杂环基，杂环氧基，-NR 6 R 7，-NR 8 COR 9，-NR 8 SO 2 R 9，-CONR 6 R -SH，-S（O）pR 1 O，-COR 1或-CO 2 R 1; 其中R 6和R 7各自独立地为H，C 1 -C 4烷基，C 3 -C 7环烷基（任选被羟基或C 1 -C 4烷氧基取代），芳基，芳基（C 1 -C 4烷基），C 2 -C 6烷氧基烷基 ，或杂环基; 或两个基团R 6和R 7与它们所连接的氮一起形成吡咯烷基，哌啶子基，吗啉代，哌嗪基或N-（C 1 -C 4烷基） - 哌嗪基; R 8是H或C 1 -C 4烷基; R 9是C 1 -C 4烷基，CF 3，芳基，芳基（C 1 -C 4烷基），芳基（C 1 -C 4烷氧基），杂环基，C 1 -C 4烷氧基或NR 6 R 7其中R 6， 和R 7如前所定义; R 1是C 1 -C 4烷基，芳基，杂环基或NR 6 R 7，其中R 6和R 7如前所定义; R 1是C 1 -C 4烷基，C 3 -C 7环烷基，芳基或杂环基; R 1是H或C 1 -C 4烷基; p为0,1或2; 或其药学上可接受的盐或其生物前体是具有用于治疗高血压，心力衰竭，肾功能不全和其它病症的利尿剂。

公开(公告)号：EP0274234B1

公开(公告)日：1991-09-11

申请号：EP87310784.1

申请日：1987-12-08

申请人： Pfizer Limited

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.

IPC分类号： C07C233/57 ,  C07D207/327 ,  C07D295/14 ,  A61K31/16 ,  A61K31/445 ,  A61K31/535 ,  A61K31/40 ,  A61K31/495 ,  C07C311/01 ,  C07C311/15

CPC分类号： C07D241/12 ,  C07D209/46 ,  C07D213/56 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D261/10 ,  C07D277/36 ,  C07D277/46 ,  C07D295/185 ,  C07D307/16 ,  C07D307/68 ,  C07D321/08 ,  C07D333/34

公开(公告)号：EP0358398A1

公开(公告)日：1990-03-14

申请号：EP89308740.3

申请日：1989-08-30

申请人： Pfizer Limited ,  PFIZER INC.

发明人： Danilewicz, John Christopher, Dr. ,  James, Keith, Dr. ,  Kobylecki, Ryszard Jurek, Dr.

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

CPC分类号： C07F7/0818 ,  C07C233/65 ,  C07C235/82 ,  C07C237/24 ,  C07C271/22 ,  C07C271/24 ,  C07C311/06 ,  C07C311/08 ,  C07C311/19 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2601/18 ,  C07D207/08 ,  C07D207/16 ,  C07D209/18 ,  C07D209/20 ,  C07D213/82 ,  C07D231/12 ,  C07D231/56 ,  C07D233/56 ,  C07D233/64 ,  C07D249/08 ,  C07D307/68 ,  C07D317/40

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.

摘要翻译： 化学式为：CHEM，其中A完成可饱和或单不饱和的5或6元碳环; R 1是H或（C 1 -C 4）烷基; R和R 4是H，（C 1 -C 6）烷基，C 3 -C 7环烷基，苄基或替代的生物不稳定酯形成基团; Y是直接键或1-6个碳原子的亚烷基; R 2是H，芳基，杂环基，R 6 CONR 5 - ，R 7 NR 5 CO - ，R 7 NR 5 SO 2 - 或R 8 SO 2 NR 5 > - ，条件是当R 2为H时，Y不是直接键，芳基或杂环基; 其中R 5是H，（C 1 -C 6）烷基或芳基（C 1 -C 6）烷基; R 6是（C 1 -C 6）烷基，芳基，芳基（C 1 -C 6）烷基，杂环基，杂环基（C 1 -C 6）烷基或式R 9 R 1基团R 其中R 9是H，OH，（C 1 -C 6）烷氧基，（C 1 -C 6）烷基，羟基（C 1 -C 6）烷基，芳基（C 1 -C 6）烷基，（C 2 -C 6） C 1 -C 6）烯基，杂环基，杂环基（C 1 -C 6）烷基，R 1 CONH，R 1，SO 2 NH-或（R 1）3 - R 1和R 1都是H或（C 1 -C 6）烷基; 或R 1是H，R 1是氨基（C 1 -C 6）烷基，咪唑基甲基，芳基，芳基（C 1 -C 6）烷基，芳基（C 1 -C 6）烷氧基（C 1 -C 6） ）烷氧基，羟基（C 1 -C 6）烷基或甲硫基（C 1 -C 6）烷基; 或两个R 1和R 1基团形成3至6元碳环或可任选被氨基，（C 2 -C 4）烷酰基或芳酰基取代的吡咯烷或哌啶环; （C1-C6）烷基，（C3-C7）环烷基，芳基，芳基（C1-C6）烷基，杂环基或杂环基（C1-C6）烷基; 每个R 1是H，（C 1 -C 6）烷基，芳基（C 1 -C 6）烷基或两个基团R 1 3形成吡咯烷基，哌啶子基，吗啉代，哌嗪基或N-（C1 -C4）烷基 - 哌嗪基; R 7是（C 1 -C 6）烷基，芳基，芳基（C 1 -C 6）烷基，杂环基，杂环基（C 1 -C 6）烷基或式R 1基团R 1 其中R 1和R 1如前所定义，R 1是（R 1）3 NCO- R 1 OCH 2 - 或R 5 OCO，其中R 1和R 3如前所定义，R 1是（ C 1 -C 6）烷基，（C 3 -C 7）环烷基或芳基（C 1 -C 6）烷基; 并且R 8是（C 1 -C 6）烷基，芳基，芳基（C 1 -C 6）烷基，杂环基或杂环基（C 1 -C 6）烷基; R 3是下式的基团：其中R 1 6是H，卤素，4-OH，4-（C 1 -C 6烷氧基），4-（C 3 -C 7环烷氧基）4- （C 2 -C 6烯氧基），4 - [（C 1 -C 6烷氧基）羰基氧基]，4 - [（C 3 -C 7环烷氧基）羰氧基]或3-（C 1 -C 4烷基）SO 2 NH- 和R 2是H，C 1 -C 4烷基，C 1 -C 4烷氧基，C 2 -C 6烷酰基或卤素; 或R 3是下式的基团：其中所述基团可任选地在稠合苯环中被C 1 -C 4烷基，C 1 -C 4烷氧基，OH，卤素或CF 3取代; 是用于治疗高血压，心力衰竭和肾功能不全的抗高血压药物。

公开(公告)号：EP0274234A3

公开(公告)日：1988-10-19

申请号：EP87310784

申请日：1987-12-08

申请人： Pfizer Limited

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.

IPC分类号： C07C103/737 ,  C07D207/327 ,  C07D295/14 ,  A61K31/16 ,  A61K31/445 ,  A61K31/535 ,  A61K31/40 ,  A61K31/495 ,  C07C143/74 ,  C07C143/78

CPC分类号： C07D241/12 ,  C07D209/46 ,  C07D213/56 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D261/10 ,  C07D277/36 ,  C07D277/46 ,  C07D295/185 ,  C07D307/16 ,  C07D307/68 ,  C07D321/08 ,  C07D333/34

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.