公开(公告)号：US5612363A

公开(公告)日：1997-03-18

申请号：US458598

申请日：1995-06-02

申请人： Raju Mohan ,  Michael M. Morrissey

发明人： Raju Mohan ,  Michael M. Morrissey

IPC分类号： A61K31/415 ,  A61K31/4166 ,  A61K31/4184 ,  A61K31/496 ,  A61K31/505 ,  A61K31/55 ,  A61P7/02 ,  C07D233/36 ,  C07D233/70 ,  C07D233/90 ,  C07D235/26 ,  C07D239/10 ,  C07D243/04 ,  C07D233/32

CPC分类号： C07D239/10 ,  C07D233/70 ,  C07D233/90 ,  C07D235/26 ,  C07D243/04

摘要： N,N-di(aryl) cyclic urea derivatives, such as the compounds of the following formula: ##STR1## wherein R.sup.1 is --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.11, --C(NH)N(H)C(O)R.sup.9, or --C(NH)N(H)C(O)OR.sup.11 ;R.sup.2 and R.sup.3 are independently hydrogen, halo, lower alkyl, lower haloalkyl, aryl, --OR.sup.11, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, --N(R.sup.11)R.sup.12, --N(H)C(O)R.sup.11, or --N(H)S(O).sub.2 R.sup.11 ;R.sup.4 is halo, lower haloalkyl, imidazolyl, --C(NH)NH.sub.2, --C(NH)NHOR.sup.11, --C(NH)N(H)C(O)R.sup.9, --C(NH)N(H)C(O)OR.sup.11, --OR.sup.11, --C(O)R.sup.13, --(CH.sub.2).sub.n C(O)OR.sup.11 (where n is 0 to 6), --C(O)N(R.sup.11)R.sup.12, or --N(R.sup.11)R.sup.12 ;R.sup.7 and R.sup.8 are independently hydrogen, lower alkyl, lower haloalkyl, 4-pyridinyl, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, or aryl (optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy, lower alkyl, lower haloalkyl, lower alkoxy and --N(R.sup.11 R.sup.12);R.sup.11 and R.sup.12 are independently hydrogen, lower alkyl, aryl or lower aralkyl; orR.sup.13 is pyrrolidinyl, 4-morpholinyl, piperazinyl, N-methylpiperazinyl, or piperidinyl; or apharmaceutically acceptable salt thereof, are disclosed herein as being inhibitors of factor Xa and thereby being useful as anticoagulants.

摘要翻译： N，N-二（芳基）环脲衍生物，例如下式的化合物：其中R 1是-C（NH）NH 2，-C（NH）N（H）OR 11，-C （NH）N（H）C（O）R 9或-C（NH）N（H）C（O）OR 11; R2和R3独立地是氢，卤素，低级烷基，低级卤代烷基，芳基，-OR11，-C（O）OR11，-C（O）N（R11）R12，-N（R11）R12，-N（H） C（O）R 11或-N（H）S（O）2 R 11; R4是卤素，低级卤代烷基，咪唑基，-C（NH）NH2，-C（NH）NHOR11，-C（NH）N（H）C（O）R9，-C（NH）N（H） ）OR11，-OR11，-C（O）R13， - （CH2）nC（O）OR11（其中n为0至6），-C（O）N（R11）R12或-N（R11）R12; R 7和R 8独立地是氢，低级烷基，低级卤代烷基，4-吡啶基，-C（O）OR 11，-C（O）N（R 11）R 12或芳基（任选被一个或多个选自 卤素，羟基，低级烷基，低级卤代烷基，低级烷氧基和-N（R 11 R 12）; R 11和R 12独立地是氢，低级烷基，芳基或低级芳烷基;或R 13是吡咯烷基，4-吗啉基，哌嗪基，N-甲基哌嗪基， 或哌啶基;或其药学上可接受的盐在本文中公开为因子Xa的抑制剂，从而可用作抗凝剂。

公开(公告)号：US6071912A

公开(公告)日：2000-06-06

申请号：US394458

申请日：1999-09-09

申请人： Monica Kochanny ,  Raju Mohan ,  Michael M. Morrissey ,  Howard P. Ng ,  Weiya Yun

发明人： Monica Kochanny ,  Raju Mohan ,  Michael M. Morrissey ,  Howard P. Ng ,  Weiya Yun

IPC分类号： C07D213/60 ,  A61K31/00 ,  A61K31/44 ,  A61K31/4427 ,  A61K31/4439 ,  A61P7/00 ,  A61P7/02 ,  C07C43/20 ,  C07C257/18 ,  C07D401/12 ,  C07D401/14 ,  A61K31/53 ,  C07D251/26

CPC分类号： C07D401/12

摘要： This invention is directed to benzamidine derivatives substituted by amino acid and hydroxy acid derivatives which are useful as anti-coagulants. This invention is also directed to pharmaceutical compositions containing the compounds of the invention, and methods of using the compounds to treat disease-states characterized by thrombotic activity.

摘要翻译： 本发明涉及由用作抗凝剂的氨基酸和羟基酸衍生物取代的苯甲脒衍生物。 本发明还涉及含有本发明化合物的药物组合物，以及使用该化合物治疗以血栓形成活性为特征的疾病状态的方法。

公开(公告)号：US5731308A

公开(公告)日：1998-03-24

申请号：US764133

申请日：1996-12-12

申请人： Raju Mohan ,  Michael M. Morrissey

发明人： Raju Mohan ,  Michael M. Morrissey

IPC分类号： A61K31/415 ,  A61K31/4166 ,  A61K31/4184 ,  A61K31/496 ,  A61K31/505 ,  A61K31/55 ,  A61P7/02 ,  C07D233/36 ,  C07D233/70 ,  C07D233/90 ,  C07D235/26 ,  C07D239/10 ,  C07D243/04

CPC分类号： C07D239/10 ,  C07D233/70 ,  C07D233/90 ,  C07D235/26 ,  C07D243/04

摘要： N,N-di(aryl) cyclic urea derivatives, such as the compounds of the following formula: ##STR1## wherein R.sup.1 is --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.11, --C(NH)N(H)C(O)R.sup.9, or --C(NH)N(H)C(O)OR.sup.11 ; R.sup.2 and R.sup.3 are independently hydrogen, halo, lower alkyl, lower haloalkyl, aryl, --OR.sup.11, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, --N(R.sup.11)R.sup.12, --N(H)C(O)R.sup.11, or --N(H)S(O).sub.2 R.sup.11 ; R.sup.4 is halo, lower haloalkyl, imidazolyl, --C (NH)NH.sub.2, --C(NH)NHOR.sup.11, --C(NH)N(H)C(O)R.sup.9, --C(NH)N(H)C(O)OR.sup.11, --OR.sup.11, --C(O)R.sup.13, --(CH.sub.2).sub.n C(O)OR.sup.11 (where n is 0 to 6), --C(O)N(R.sup.11)R.sup.12, or --N(R.sup.11)R.sup.12 ; R.sup.7 and R.sup.8 are independently hydrogen, lower alkyl, lower haloalkyl, 4-pyridinyl, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, or aryl (optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy, lower alkyl, lower haloalkyl, lower alkoxy and --N(R.sup.11)R.sup.12); R.sup.11 and R.sup.12 are independently hydrogen, lower alkyl, aryl or lower aralkyl; or R.sup.13 is pyrrolidinyl, 4-morpholinyl, piperazinyl, N-methylpiperazinyl, or piperidinyl; or a pharmaceutically acceptable salt thereof, are disclosed herein as being inhibitors of factor Xa and thereby being useful as anticoagulants.

摘要翻译： N，N-二（芳基）环脲衍生物，例如下式的化合物：其中R 1是-C（NH）NH 2，-C（NH）N（H）OR 11，-C （NH）N（H）C（O）R 9或-C（NH）N（H）C（O）OR 11; R2和R3独立地是氢，卤素，低级烷基，低级卤代烷基，芳基，-OR11，-C（O）OR11，-C（O）N（R11）R12，-N（R11）R12，-N（H） C（O）R 11或-N（H）S（O）2 R 11; R4是卤素，低级卤代烷基，咪唑基，-C（NH）NH2，-C（NH）NHOR11，-C（NH）N（H）C（O）R9，-C（NH）N（H） ）OR11，-OR11，-C（O）R13， - （CH2）nC（O）OR11（其中n为0至6），-C（O）N（R11）R12或-N（R11）R12; R 7和R 8独立地是氢，低级烷基，低级卤代烷基，4-吡啶基，-C（O）OR 11，-C（O）N（R 11）R 12或芳基（任选被一个或多个选自 卤素，羟基，低级烷基，低级卤代烷基，低级烷氧基和-N（R 11）R 12）; R 11和R 12独立地是氢，低级烷基，芳基或低级芳烷基; 或R 13为吡咯烷基，4-吗啉基，哌嗪基，N-甲基哌嗪基或哌啶基; 或其药学上可接受的盐在本文中公开为因子Xa的抑制剂，从而可用作抗凝血剂。

公开(公告)号：US5726198A

公开(公告)日：1998-03-10

申请号：US766152

申请日：1996-12-12

申请人： Raju Mohan ,  Michael M. Morrissey

发明人： Raju Mohan ,  Michael M. Morrissey

IPC分类号： A61K31/415 ,  A61K31/4166 ,  A61K31/4184 ,  A61K31/496 ,  A61K31/505 ,  A61K31/55 ,  A61P7/02 ,  C07D233/36 ,  C07D233/70 ,  C07D233/90 ,  C07D235/26 ,  C07D239/10 ,  C07D243/04 ,  A61K31/535 ,  C07D413/10

CPC分类号： C07D239/10 ,  C07D233/70 ,  C07D233/90 ,  C07D235/26 ,  C07D243/04

摘要： N,N-di(aryl) cyclic urea derivatives, such as the compounds of the following formula: ##STR1## wherein R.sup.1 is --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.11, --C(NH)N(H)C(O)R.sup.9, or --C(NH)N(H)C(O)OR.sup.11 ; R.sup.2 and R.sup.3 are independently hydrogen, halo, lower alkyl, lower haloalkyl, aryl, --OR.sup.11, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, --N(R.sup.11)R.sup.12, --N(H)C(O)R.sup.11, or --N(H)S(O).sub.2 R.sup.11 ; R.sup.4 is halo, lower haloalkyl, imidazolyl, --C(NH)NH.sub.2, --C(NH)NHOR.sup.11, --C(NH)N(H)C(O)R.sup.9, --C(NH)N(H)C(O)OR.sup.11, --OR.sup.11, --C(O)R.sup.13, --(CH.sub.2).sub.n C(O)OR.sup.11 (where n is 0 to 6), --C(O)N(R.sup.11)R.sup.12, or --N(R.sup.11)R.sup.12 ; R.sup.7 and R.sup.8 are independently hydrogen, lower alkyl, lower haloalkyl, 4-pyridinyl, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, or aryl (optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy, lower alkyl, lower haloalkyl, lower alkoxy and --N(R.sup.11)R.sup.12); R.sup.11 and R.sup.12 are independently hydrogen, lower alkyl, aryl or lower aralkyl; or R.sup.13 is pyrrolidinyl, 4-morpholinyl, piperazinyl, N-methylpiperazinyl, or piperidinyl; or a pharmaceutically acceptable salt thereof, are disclosed herein as being inhibitors of factor Xa and thereby being useful as anticoagulants.

公开(公告)号：US5726173A

公开(公告)日：1998-03-10

申请号：US762888

申请日：1996-12-12

申请人： Raju Mohan ,  Michael M. Morrissey

发明人： Raju Mohan ,  Michael M. Morrissey

IPC分类号： A61K31/415 ,  A61K31/4166 ,  A61K31/4184 ,  A61K31/496 ,  A61K31/505 ,  A61K31/55 ,  A61P7/02 ,  C07D233/36 ,  C07D233/70 ,  C07D233/90 ,  C07D235/26 ,  C07D239/10 ,  C07D243/04 ,  A61K31/535 ,  C07D403/10 ,  C07D413/10

CPC分类号： C07D239/10 ,  C07D233/70 ,  C07D233/90 ,  C07D235/26 ,  C07D243/04

摘要： N,N-di(aryl) cyclic urea derivatives, such as the compounds of the following formula: ##STR1## wherein R.sup.1 is --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.11, --C(NH)N(H)C(O)R.sup.9, or --C(NH)N(H)C(O)OR.sup.11 ; R.sup.2 and R.sup.3 are independently hydrogen, halo, lower alkyl, lower haloalkyl, aryl, --OR.sup.11, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, --N(R.sup.11)R.sup.12, --N(H)C(O)R.sup.11, or --N(H)S(O).sub.2 R.sup.11 ; R.sup.4 is halo, lower haloalkyl, imidazolyl, --C(NH)NH.sub.2, --C(NH)NHOR.sup.11, --C(NH)N(H)C(O)R.sup.9, --C(NH)N(H)C(O)OR.sup.11, --OR.sup.11, --C(O)R.sup.13, --(CH.sub.2).sub.n C(O)OR.sup.11 (where n is 0 to 6), --C(O)N(R.sup.11)R.sup.12, or --N(R.sup.11)R.sup.12 ; R.sup.7 and R.sup.8 are independently hydrogen, lower alkyl, lower haloalkyl, 4-pyridinyl, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, or aryl (optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy, lower alkyl, lower haloalkyl, lower alkoxy and --N(R.sup.11)R.sup.12); R.sup.11 and R.sup.12 are independently hydrogen, lower alkyl, aryl or lower aralkyl; or R.sup.13 is pyrrolidinyl, 4-morpholinyl, piperazinyl, N-methylpiperazinyl, or piperidinyl; or a pharmaceutically acceptable salt thereof, are disclosed herein as being inhibitors of factor Xa and thereby being useful as anticoagulants.

摘要翻译： N，N-二（芳基）环脲衍生物，例如下式的化合物：其中R 1是-C（NH）NH 2，-C（NH）N（H）OR 11，-C （NH）N（H）C（O）R 9或-C（NH）N（H）C（O）OR 11; R2和R3独立地是氢，卤素，低级烷基，低级卤代烷基，芳基，-OR11，-C（O）OR11，-C（O）N（R11）R12，-N（R11）R12，-N（H） C（O）R 11或-N（H）S（O）2 R 11; R4是卤素，低级卤代烷基，咪唑基，-C（NH）NH2，-C（NH）NHOR11，-C（NH）N（H）C（O）R9，-C（NH）N（H） ）OR11，-OR11，-C（O）R13， - （CH2）nC（O）OR11（其中n为0至6），-C（O）N（R11）R12或-N（R11）R12; R 7和R 8独立地是氢，低级烷基，低级卤代烷基，4-吡啶基，-C（O）OR 11，-C（O）N（R 11）R 12或芳基（任选被一个或多个选自 卤素，羟基，低级烷基，低级卤代烷基，低级烷氧基和-N（R 11）R 12）; R 11和R 12独立地是氢，低级烷基，芳基或低级芳烷基; 或R 13为吡咯烷基，4-吗啉基，哌嗪基，N-甲基哌嗪基或哌啶基; 或其药学上可接受的盐在本文中公开为因子Xa的抑制剂，从而可用作抗凝血剂。

公开(公告)号：US5994375A

公开(公告)日：1999-11-30

申请号：US599834

申请日：1996-02-12

申请人： Monica Kochanny ,  Raju Mohan ,  Michael M. Morrissey ,  Howard P. Ng

发明人： Monica Kochanny ,  Raju Mohan ,  Michael M. Morrissey ,  Howard P. Ng

IPC分类号： C07D213/60 ,  A61K31/00 ,  A61K31/44 ,  A61K31/4427 ,  A61K31/4439 ,  A61P7/00 ,  A61P7/02 ,  C07C43/20 ,  C07C257/18 ,  C07D401/12 ,  C07D401/14 ,  C07D401/10

CPC分类号： C07D401/12

摘要： This invention is directed to benzamidine derivatives substituted by amino acid and hydroxy acid derivatives which are useful as anti-coagulants. This invention is also directed to pharmaceutical compositions containing the compounds of the invention, and methods of using the compounds to treat disease-states characterized by thrombotic activity.

公开(公告)号：US5863914A

公开(公告)日：1999-01-26

申请号：US764028

申请日：1996-12-12

申请人： Raju Mohan ,  Michael M. Morrissey

发明人： Raju Mohan ,  Michael M. Morrissey

IPC分类号： A61K31/415 ,  A61K31/4166 ,  A61K31/4184 ,  A61K31/496 ,  A61K31/505 ,  A61K31/55 ,  A61P7/02 ,  C07D233/36 ,  C07D233/70 ,  C07D233/90 ,  C07D235/26 ,  C07D239/10 ,  C07D243/04 ,  A61K31/535 ,  A61K31/445 ,  A61K31/495 ,  A61K31/50

CPC分类号： C07D239/10 ,  C07D233/70 ,  C07D233/90 ,  C07D235/26 ,  C07D243/04

摘要： N,N-di(aryl) cyclic urea derivatives, such as the compounds of the following formula: ##STR1## wherein R.sup.1 is --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.11, --C(NH)N(H)C(O)R.sup.9, or --C(NH)N(H)C(O)OR.sup.11 ;R.sup.2 and R.sup.3 are independently hydrogen, halo, lower alkyl, lower haloalkyl, aryl, --OR.sup.11, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, --N(R.sup.11)R.sup.12, --N(H)C(O)R.sup.11, or --N(H)S(O).sub.2 R.sup.11 ;R.sup.4 is halo, lower haloalkyl, imidazolyl, --C(NH)NH.sub.2, --C(NH)NHOR.sup.11, --C(NH)N(H)C(O)R.sup.9, --C(NH)N(H)C(O)OR.sup.11, --OR.sup.11, --C(O)R.sup.13, --(CH.sub.2).sub.n C(O)OR.sup.11 (where n is 0 to 6), --C(O)N(R.sup.11)R.sup.12, or --N(.sup.11)R.sup.12 ;R.sup.7 and R.sup.8 are independently hydrogen, lower alkyl, lower haloalkyl, 4-pyridinyl, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, or aryl (optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy, lower alkyl, lower haloalkyl, lower alkoxy and --N(R.sup.11)R.sup.12);R.sup.11 and R.sup.12 are independently hydrogen, lower alkyl, aryl or lower aralkyl; orR.sup.13 is pyrrolidinyl, 4-morpholinyl, piperazinyl, N-methylpiperazinyl, or piperidinyl; or a pharmaceutically acceptable salt thereof, are disclosed herein as being inhibitors of factor Xa and thereby being useful as anticoagulants.

摘要翻译： N，N-二（芳基）环脲衍生物，例如下式的化合物：其中R 1是-C（NH）NH 2，-C（NH）N（H）OR 11，-C （NH）N（H）C（O）R 9或-C（NH）N（H）C（O）OR 11; R2和R3独立地是氢，卤素，低级烷基，低级卤代烷基，芳基，-OR11，-C（O）OR11，-C（O）N（R11）R12，-N（R11）R12，-N（H） C（O）R 11或-N（H）S（O）2 R 11; R4是卤素，低级卤代烷基，咪唑基，-C（NH）NH2，-C（NH）NHOR11，-C（NH）N（H）C（O）R9，-C（NH）N（H） ）OR 11，-OR 11，-C（O）R 13， - （CH 2）n C（O）OR 11（其中n为0至6），-C（O）N（R 11）R 12或-N（11）R 12; R 7和R 8独立地是氢，低级烷基，低级卤代烷基，4-吡啶基，-C（O）OR 11，-C（O）N（R 11）R 12或芳基（任选被一个或多个选自 卤素，羟基，低级烷基，低级卤代烷基，低级烷氧基和-N（R 11）R 12）; R 11和R 12独立地是氢，低级烷基，芳基或低级芳烷基; 或R 13为吡咯烷基，4-吗啉基，哌嗪基，N-甲基哌嗪基或哌啶基; 或其药学上可接受的盐在本文中公开为因子Xa的抑制剂，从而可用作抗凝血剂。

公开(公告)号：US5859005A

公开(公告)日：1999-01-12

申请号：US764500

申请日：1996-12-12

申请人： Raju Mohan ,  Michael M. Morrissey

发明人： Raju Mohan ,  Michael M. Morrissey

IPC分类号： A61K31/415 ,  A61K31/4166 ,  A61K31/4184 ,  A61K31/496 ,  A61K31/505 ,  A61K31/55 ,  A61P7/02 ,  C07D233/36 ,  C07D233/70 ,  C07D233/90 ,  C07D235/26 ,  C07D239/10 ,  C07D243/04 ,  A61K31/495 ,  A61K31/50 ,  A61K31/535

CPC分类号： C07D239/10 ,  C07D233/70 ,  C07D233/90 ,  C07D235/26 ,  C07D243/04

摘要： N,N-di(aryl) cyclic urea derivatives, such as the compounds of the following formula: ##STR1## wherein R.sup.1 is --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.11, --C(NH)N(H)C(O)R.sup.9, or --C(NH)N(H)C(O)OR.sup.11 ;R.sup.2 and R.sup.3 are independently hydrogen, halo, lower alkyl, lower haloalkyl, aryl, --OR.sup.11, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, --N(R.sup.11)R.sup.12, --N(H)C(O)R.sup.11, or --N(H)S(O).sub.2 R.sup.11 ;R.sup.4 is halo, lower haloalkyl, imidazolyl, --C(NH)NH.sub.2, --C(NH)NHOR.sup.11, --C(NH)N(H)C(O)R.sup.9, --C(NH)N(H)C(O)OR.sup.11, --OR.sup.11, --C(O)R.sup.13, --(CH.sub.2).sub.n C(O)OR.sup.11 (where n is 0 to 6), --C(O)N(R.sup.11)R.sup.12, or --N(R.sup.11)R.sup.12 ;R.sup.7 and R.sup.8 are independently hydrogen, lower alkyl, lower haloalkyl, 4-pyridinyl, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, or aryl (optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy, lower alkyl, lower haloalkyl, lower alkoxy and --N(R.sup.11)R.sup.12);R.sup.11 and R.sup.12 are independently hydrogen, lower alkyl, aryl or lower aralkyl; orR.sup.13 is pyrrolidinyl, 4-morpholinyl, piperazinyl, N-methylpiperazinyl, or piperidinyl; or a pharmaceutically acceptable salt thereof, are disclosed herein as being inhibitors of factor Xa and thereby being useful as anticoagulants.

摘要翻译： N，N-二（芳基）环脲衍生物，例如下式的化合物：其中R 1是-C（NH）NH 2，-C（NH）N（H）OR 11，-C （NH）N（H）C（O）R 9或-C（NH）N（H）C（O）OR 11; R2和R3独立地是氢，卤素，低级烷基，低级卤代烷基，芳基，-OR11，-C（O）OR11，-C（O）N（R11）R12，-N（R11）R12，-N（H） C（O）R 11或-N（H）S（O）2 R 11; R4是卤素，低级卤代烷基，咪唑基，-C（NH）NH2，-C（NH）NHOR11，-C（NH）N（H）C（O）R9，-C（NH）N（H） ）OR11，-OR11，-C（O）R13， - （CH2）nC（O）OR11（其中n为0至6），-C（O）N（R11）R12或-N（R11）R12; R 7和R 8独立地是氢，低级烷基，低级卤代烷基，4-吡啶基，-C（O）OR 11，-C（O）N（R 11）R 12或芳基（任选被一个或多个选自 卤素，羟基，低级烷基，低级卤代烷基，低级烷氧基和-N（R 11）R 12）; R 11和R 12独立地是氢，低级烷基，芳基或低级芳烷基; 或R 13为吡咯烷基，4-吗啉基，哌嗪基，N-甲基哌嗪基或哌啶基; 或其药学上可接受的盐在本文中公开为因子Xa的抑制剂，从而可用作抗凝血剂。

公开(公告)号：US5731311A

公开(公告)日：1998-03-24

申请号：US764374

申请日：1996-12-12

申请人： Raju Mohan ,  Michael M. Morrissey

发明人： Raju Mohan ,  Michael M. Morrissey

IPC分类号： A61K31/415 ,  A61K31/4166 ,  A61K31/4184 ,  A61K31/496 ,  A61K31/505 ,  A61K31/55 ,  A61P7/02 ,  C07D233/36 ,  C07D233/70 ,  C07D233/90 ,  C07D235/26 ,  C07D239/10 ,  C07D243/04 ,  A61K31/535 ,  A61K31/495 ,  C07D403/10 ,  C07D413/10

CPC分类号： C07D239/10 ,  C07D233/70 ,  C07D233/90 ,  C07D235/26 ,  C07D243/04

摘要： N,N-di(aryl) cyclic urea derivatives, such as the compounds of the following formula: ##STR1## wherein R.sup.1 is --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.11, --C(NH)N(H)C(O)R.sup.9, or --C(NH)N(H)C(O)OR.sup.11 ; R.sup.2 and R.sup.3 are independently hydrogen, halo, lower alkyl, lower haloalkyl, aryl, --OR.sup.11, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, --N(R.sup.11)R.sup.12, --N(H)C(O)R.sup.11, or --N(H)S(O).sub.2 R.sup.11 ; R.sup.4 is halo, lower haloalkyl, imidazolyl, --C(NH)NH.sub.2, --C(NH)NHOR.sup.11, --C(NH)N(H)C(O)R.sup.9, --C(NH)N(H)C(O)OR.sup.11, --OR.sup.11, --C(O)R.sup.13, --(CH.sub.2).sub.n C(O)OR.sup.11 (where n is 0 to 6), --C(O)N(R.sup.11)R.sup.12, or --N(R.sup.11)R.sup.12 ; R.sup.7 and R.sup.8 are independently hydrogen, lower alkyl, lower haloalkyl, 4-pyridinyl, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, or aryl (optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy, lower alkyl, lower haloalkyl, lower alkoxy and --N(R.sup.11)R.sup.12); R.sup.11 and R.sup.12 are independently hydrogen, lower alkyl, aryl or lower aralkyl; or R.sup.13 is pyrrolidinyl, 4-morpholinyl, piperazinyl, N-methylpiperazinyl, or piperidinyl; or a pharmaceutically acceptable salt thereof, are disclosed herein as being inhibitors of factor Xa and thereby being useful as anticoagulants.

公开(公告)号：US5728697A

公开(公告)日：1998-03-17

申请号：US766373

申请日：1996-12-12

申请人： Raju Mohan ,  Michael M. Morrissey

发明人： Raju Mohan ,  Michael M. Morrissey

IPC分类号： A61K31/415 ,  A61K31/4166 ,  A61K31/4184 ,  A61K31/496 ,  A61K31/505 ,  A61K31/55 ,  A61P7/02 ,  C07D233/36 ,  C07D233/70 ,  C07D233/90 ,  C07D235/26 ,  C07D239/10 ,  C07D243/04 ,  A61K31/535 ,  C07D403/10 ,  C07D413/10

CPC分类号： C07D239/10 ,  C07D233/70 ,  C07D233/90 ,  C07D235/26 ,  C07D243/04

摘要： N,N-di(aryl) cyclic urea derivatives, such as the compounds of the following formula: ##STR1## wherein R.sup.1 is --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.11, --C(NH)N(H)C(O)R.sup.9, or --C(NH)N(H)C(O)OR.sup.11 ; R.sup.2 and R.sup.3 are independently hydrogen, halo, lower alkyl, lower haloalkyl, aryl, --OR.sup.11, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, --N(R.sup.11)R.sup.12, --N(H)C(O)R.sup.11, or --N(H)S(O).sub.2 R.sup.11 ; R.sup.4 is halo, lower haloalkyl, imidazolyl, --C(NH)NH.sub.2, --C(NH)NHOR.sup.11, --(CH.sub.2).sub.n C(O)OR.sup.11 (where n is 0 to 6), --C(O)N(R.sup.11)R.sup.12, or --N(R.sup.11)R.sup.12 ; R.sup.7 and R.sup.8 are independently hydrogen, lower alkyl, lower haloalkyl, 4-pyridinyl, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, or aryl (optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy, lower alkyl, lower haloalkyl, lower alkoxy and --N(R.sup.11)R.sup.12); R.sup.11 and R.sup.12 are independently hydrogen, lower alkyl, aryl or lower aralkyl; or R.sup.13 is pyrrolidinyl, 4-morpholinyl, piperazinyl, N-methylpiperazinyl, or piperidinyl; or a pharmaceutically acceptable salt thereof, are disclosed herein as being inhibitors of factor Xa and thereby being useful as anticoagulants.

摘要翻译： N，N-二（芳基）环脲衍生物，例如下式的化合物：其中R 1是-C（NH）NH 2，-C（NH）N（H）OR 11，-C （NH）N（H）C（O）R 9或-C（NH）N（H）C（O）OR 11; R2和R3独立地是氢，卤素，低级烷基，低级卤代烷基，芳基，-OR11，-C（O）OR11，-C（O）N（R11）R12，-N（R11）R12，-N（H） C（O）R 11或-N（H）S（O）2 R 11; R4是卤素，低级卤代烷基，咪唑基，-C（NH）NH2，-C（NH）NHOR11， - （CH2）nC（O）OR11（其中n为0至6），-C（O）N（R11） R12或-N（R11）R12; R 7和R 8独立地是氢，低级烷基，低级卤代烷基，4-吡啶基，-C（O）OR 11，-C（O）N（R 11）R 12或芳基（任选被一个或多个选自 卤素，羟基，低级烷基，低级卤代烷基，低级烷氧基和-N（R 11）R 12）; R 11和R 12独立地是氢，低级烷基，芳基或低级芳烷基; 或R 13为吡咯烷基，4-吗啉基，哌嗪基，N-甲基哌嗪基或哌啶基; 或其药学上可接受的盐在本文中公开为因子Xa的抑制剂，从而可用作抗凝血剂。