公开(公告)号：US06602895B2

公开(公告)日：2003-08-05

申请号：US10150698

申请日：2002-05-16

Applicant: Robert A. Galemmo, Jr. ,  Celia Dominguez ,  John M. Fevig ,  Qi Han ,  Patrick Y. Lam ,  Donald J. P. Pinto ,  James R. Pruitt ,  Mimi L. Quan

Inventor： Robert A. Galemmo, Jr. ,  Celia Dominguez ,  John M. Fevig ,  Qi Han ,  Patrick Y. Lam ,  Donald J. P. Pinto ,  James R. Pruitt ,  Mimi L. Quan

IPC: A61K3141

CPC classification number: C07D257/04 ,  C07D231/14 ,  C07D277/56 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D413/12

Abstract: The present application describes inhibitors of factor Xa with a neutral P1 specificity group of formula I: or pharmaceutically acceptable salt forms thereof, wherein R and E may be groups such as methoxy and halo.

公开(公告)号：US06521614B1

公开(公告)日：2003-02-18

申请号：US09305561

申请日：1999-05-05

Applicant: Thomas Peter Maduskuie, Jr. ,  Robert Anthony Galemmo, Jr. ,  Celia Dominguez ,  Mimi Lifen Quan ,  Karen Anita Rossi ,  Petrus Fredericus Wilhelmus Stouten ,  Jung-Hui Sun ,  Brian Lloyd Wells

Inventor： Thomas Peter Maduskuie, Jr. ,  Robert Anthony Galemmo, Jr. ,  Celia Dominguez ,  Mimi Lifen Quan ,  Karen Anita Rossi ,  Petrus Fredericus Wilhelmus Stouten ,  Jung-Hui Sun ,  Brian Lloyd Wells

IPC: C07D24304

CPC classification number: C07D401/04 ,  C07D243/04 ,  C07D401/14 ,  C07D409/14 ,  C07D413/04 ,  C07D417/14

Abstract: The present application describes N-(amidinophenyl)cyclourea analogs of formula I: which are useful as inhibitors of factor Xa.

Abstract translation: 本申请描述了式I的N-（脒基苯基）环脲类似物：其可用作因子Xa的抑制剂。

公开(公告)号：US06207697B1

公开(公告)日：2001-03-27

申请号：US09149826

申请日：1998-09-08

Applicant: Qi Han ,  Celia Dominguez ,  Eugene C. Amparo ,  Jeongsook M. Park ,  Mimi L. Quan ,  Karen A. Rossi

Inventor： Qi Han ,  Celia Dominguez ,  Eugene C. Amparo ,  Jeongsook M. Park ,  Mimi L. Quan ,  Karen A. Rossi

IPC: C07D20934

CPC classification number: C07D263/58 ,  C07D209/34 ,  C07D235/26 ,  C07D241/44

Abstract: The present application describes inhibitors of factor Xa of formula I: or pharmaceutically acceptable salt forms thereof, wherein W, W1, W2, and W3 may be N or C and J, Ja, and Jb combine to form a substituted carbocycle or heterocycle.

Abstract translation: 本申请描述了式I的因子Xa或其药学上可接受的盐形式的抑制剂，其中W，W 1，W 2和W 3可以是N或C并且J，J a和J b结合形成取代的碳环或杂环。

公开(公告)号：US6043257A

公开(公告)日：2000-03-28

申请号：US176037

申请日：1998-10-21

Applicant: Celia Dominguez ,  Qi Han ,  Daniel Emmett Duffy ,  Jeongsook Maria Park ,  Mimi Lifen Quan ,  Karen Anita Rossi ,  Ruth Richmond Wexler

Inventor： Celia Dominguez ,  Qi Han ,  Daniel Emmett Duffy ,  Jeongsook Maria Park ,  Mimi Lifen Quan ,  Karen Anita Rossi ,  Ruth Richmond Wexler

IPC: C07D209/08 ,  C07D209/12 ,  C07D209/18 ,  C07D231/56 ,  C07D235/06 ,  C07D307/81 ,  C07D333/58 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D405/14 ,  C07D409/14 ,  C07D471/04 ,  A01N43/40 ,  A01N43/38 ,  C07D235/26

CPC classification number: C07D401/06 ,  C07D209/08 ,  C07D209/12 ,  C07D209/18 ,  C07D231/56 ,  C07D235/06 ,  C07D307/81 ,  C07D333/58 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D405/14 ,  C07D409/14 ,  C07D471/04

Abstract: The present application describes amidinoindoles, amidinoazoles, and analogs thereof of formula I: ##STR1## wherein W, W.sup.1, W.sup.2, and W.sup.3 are selected from CH and N, provided that one of W.sup.1 and W.sup.2 is C(C(.dbd.NH)NH.sub.2) and at most two of W, W.sup.1, W.sup.2, and W.sup.3 are N and one of J.sup.a and J.sup.b is substituted by --(CH.sub.2).sub.n --Z--A--B, which are useful as inhibitors of factor Xa or thrombin.

Abstract translation: 本申请描述了式I的脒基吲哚，脒基吖嗪及其类似物：其中W，W 1，W 2和W 3选自CH和N，条件是W 1和W 2之一为C（C（= NH）NH 2） W，W1，W2和W3中的大多数为N，并且Ja和Jb中的一个被 - （CH 2）n ZAB取代，其可用作因子Xa或凝血酶的抑制剂。

公开(公告)号：US5886191A

公开(公告)日：1999-03-23

申请号：US916736

申请日：1997-08-18

Applicant: Celia Dominguez ,  Qi Han ,  Daniel Emmett Duffy ,  Jeongsook Maria Park ,  Mimi Lifen Quan ,  Karen Anita Rossi ,  Ruth Richmond Wexler

Inventor： Celia Dominguez ,  Qi Han ,  Daniel Emmett Duffy ,  Jeongsook Maria Park ,  Mimi Lifen Quan ,  Karen Anita Rossi ,  Ruth Richmond Wexler

IPC: C07D209/08 ,  C07D209/12 ,  C07D209/18 ,  C07D231/56 ,  C07D235/06 ,  C07D307/81 ,  C07D333/58 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D405/14 ,  C07D409/14 ,  C07D471/04 ,  C07D209/04 ,  C07D209/14 ,  C07D209/26 ,  C07D333/52

CPC classification number: C07D401/06 ,  C07D209/08 ,  C07D209/12 ,  C07D209/18 ,  C07D231/56 ,  C07D235/06 ,  C07D307/81 ,  C07D333/58 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D405/14 ,  C07D409/14 ,  C07D471/04

Abstract: The present application describes amidinoindoles, amidinoazoles, and analogs thereof of formula I: ##STR1## wherein W, W.sup.1, W.sup.2, and W.sup.3 are selected from CH and N, provided that one of W.sup.1 and W.sup.2 is C(C(.dbd.NH)NH.sub.2) and at most two of W, W.sup.1, W.sup.2, and W.sup.3 are N and one of J.sup.a and J.sup.b is substituted by --(CH.sub.2).sub.n --Z--A--B, which are useful as inhibitors of factor Xa or thrombin.

Abstract translation: 本申请描述了由式I表示的脒基吲哚，脒基吖嗪及其类似物：CH和N，条件是W1和W2之一为C（C（= NH）NH 2），W 2，W 2，W 2和 W3为N，Ja和Jb中的一个被 - （CH 2）n ZAB取代，其可用作因子Xa或凝血酶的抑制剂。

公开(公告)号：US5856318A

公开(公告)日：1999-01-05

申请号：US910302

申请日：1997-08-11

Applicant: Wayne Bowen ,  Brian R. de Costa ,  Celia Dominguez ,  Xiao-Shu He ,  Kenner C. Rice

Inventor： Wayne Bowen ,  Brian R. de Costa ,  Celia Dominguez ,  Xiao-Shu He ,  Kenner C. Rice

IPC: C07D207/14 ,  C07D211/56 ,  C07D223/12 ,  C07D409/06 ,  A61K31/33 ,  A61K31/55 ,  C07D295/00 ,  C07D405/00

CPC classification number: C07D409/06 ,  C07D207/14 ,  C07D211/56 ,  C07D223/12

Abstract: Certain nitrogen-containing cyclohetero cycloalkylaminoaryl compounds are described for treatment of CNS disorders such as cerebral ischemia, psychoses and convulsions. Compounds of particular interest are of the formula: ##STR1## wherein each of R.sup.1, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 is independently selected from hydrido, lower alkyl, benzyl, and haloloweralkyl;wherein each of R.sup.2, R.sup.3 and R.sup.8 through R.sup.11 is independently selected from hydrido, hydroxy, loweralkyl, benzyl, phenoxy, benzyloxy and haloloweralkyl; wherein n is an integer of from four to six; wherein m is an integer of from two to four; wherein A is selected from phenyl, naphthyl, benzothienyl, benzofuranyl and thienyl; wherein any of the foregoing A groups can be further substituted with one or more substituents independently selected from hydrido, hydroxy, loweralkyl, loweralkoxy, halo, haloloweralkyl, amino, monoloweralkylamino and diloweralkylamino; or a pharmaceutically acceptable salt thereof.

Abstract translation: 描述某些含氮环杂环烷基氨基芳基化合物用于治疗中枢神经系统疾病如脑缺血，精神病和抽搐。 特别感兴趣的化合物具有下式：其中R 1，R 4，R 5，R 6和R 7各自独立地选自氢，低级烷基，苄基和卤代低级烷基; 其中R2，R3和R8至R11各自独立地选自氢，羟基，低级烷基，苄基，苯氧基，苄氧基和卤代低级烷基; 其中n为4-6的整数; 其中m是2至4的整数; 其中A选自苯基，萘基，苯并噻吩基，苯并呋喃基和噻吩基; 其中前述A基团中的任一个可以进一步被一个或多个独立地选自氢，羟基，低级烷基，低级烷氧基，卤素，卤代低级烷基，氨基，单低级烷基氨基和二低级烷基氨基的取代基取代。 或其药学上可接受的盐。

公开(公告)号：US5679679A

公开(公告)日：1997-10-21

申请号：US348654

申请日：1994-12-02

Applicant: Wayne Bowen ,  Brian R. de Costa ,  Celia Dominguez ,  Xiao-Shu He ,  Kenner C. Rice

Inventor： Wayne Bowen ,  Brian R. de Costa ,  Celia Dominguez ,  Xiao-Shu He ,  Kenner C. Rice

IPC: A61K31/495 ,  C07D471/04 ,  C07D487/04 ,  C07D31/495 ,  C07D31/55

CPC classification number: C07D471/04 ,  A61K31/495 ,  C07D487/04

Abstract: Certain aralkyl diazabicyloalkyl compounds are described for treatment of CNS disorders such as cerebral ischemia, psychoses and convulsions. Compounds of particular interest are of the formula: ##STR1## wherein: each of R.sup.1, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 is independently selected from the group consisting of hydrido, loweralkyl, benzyl and haloloweralkyl; each of R.sup.2, R.sup.3, and R.sup.8 through R.sup.11 is independently selected from the group consisting of hydrido, hydroxy, loweralkyl, benzyl, phenoxy, benzyloxy and haloloweralkyl; n is an integer of from three to four; m is an integer of two; A is selected from the group consisting of phenyl, naphthyl, benzothienyl, benzofuranyl and thienyl and wherein any of the foregoing A groups can be further substituted with one or more substituents independently selected from the group consisting of hydrido, hydroxy, loweralkyl, loweralkoxy, halo, haloloweralkyl, amino, monoloweralkylamino and diloweralkylamino; or a pharmaceutically acceptable salt thereof.

Abstract translation: 描述了某些芳烷基二氮杂双环烷基化合物用于治疗中枢神经系统疾病如脑缺血，精神病和抽搐。 特别感兴趣的化合物具有下式：其中：R 1，R 4，R 5，R 6和R 7各自独立地选自氢，低级烷基，苄基和卤代低级烷基; R 2，R 3和R 8至R 11各自独立地选自氢，羟基，低级烷基，苄基，苯氧基，苄氧基和卤代低级烷基; n是3至4的整数; m是2的整数; A选自苯基，萘基，苯并噻吩基，苯并呋喃基和噻吩基，其中任何前述A基团可以进一步被一个或多个独立地选自羟基，羟基，低级烷基，低级烷氧基，卤代 ，卤代低级烷基，氨基，单低级烷基氨基和二低级烷基氨基; 或其药学上可接受的盐。

公开(公告)号：US5679673A

公开(公告)日：1997-10-21

申请号：US344304

申请日：1994-11-21

Applicant: Wayne Bowen ,  Brian R. de Costa ,  Celia Dominguez ,  Xiao-Shu He ,  Kenner C. Rice

Inventor： Wayne Bowen ,  Brian R. de Costa ,  Celia Dominguez ,  Xiao-Shu He ,  Kenner C. Rice

IPC: C07D453/02 ,  C07D487/08 ,  A61K31/55 ,  C07D471/08

CPC classification number: C07D487/08 ,  C07D453/02

Abstract: Certain aralkyl diazabicycloalkyl compounds are described for treatment of CNS disorders such as cerebral ischemia, psychoses and convulsions. Compounds of particular interest are of the formula: ##STR1## wherein each of R, R.sup.1, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 is independently selected from hydrido, lower-alkyl, benzyl, and haloloweralkyl; wherein each of R.sup.2, R.sup.3 and R.sup.10 through R.sup.13 is independently selected from hydrido, hydroxy, loweralkyl, benzyl, phenoxy, benzyloxy and haloloweralkyl; wherein each of R.sup.8 and R.sup.9 is selected from hydrido, loweralkyl, benzyl and haloloweralkyl; wherein m is an integer of from two to four; wherein A is selected from phenyl, naphthyl, benzothiophenyl, benzofuranyl and thienyl; wherein any of the foregoing A groups can be further substituted with one or more substituents independently selected from hydrido, hydroxy, loweralkyl, loweralkoxy, halo, haloloweralkyl, amino, monoloweralkylamino and diloweralkylamino; or a pharmaceutically acceptable salt thereof.

Abstract translation: 描述了某些芳烷基二氮杂双环烷基化合物用于治疗中枢神经系统疾病如脑缺血，精神病和抽搐。 特别感兴趣的化合物具有下式：其中R，R 1，R 4，R 5，R 6和R 7各自独立地选自氢，低级烷基，苄基和卤代低级烷基; 其中R2，R3和R10至R13各自独立地选自氢，羟基，低级烷基，苄基，苯氧基，苄氧基和卤代低级烷基; 其中R8和R9各自选自氢，低级烷基，苄基和卤代低级烷基; 其中m是2至4的整数; 其中A选自苯基，萘基，苯并噻吩基，苯并呋喃基和噻吩基; 其中前述A基团中的任一个可以进一步被一个或多个独立地选自氢，羟基，低级烷基，低级烷氧基，卤素，卤代低级烷基，氨基，单低级烷基氨基和二低级烷基氨基的取代基取代。 或其药学上可接受的盐。

公开(公告)号：US5346908A

公开(公告)日：1994-09-13

申请号：US904354

申请日：1992-06-25

Applicant: Wayne Bowen ,  Brian R. de Costa ,  Celia Dominguez ,  Xiao-Shu He ,  Kenner C. Rice

Inventor： Wayne Bowen ,  Brian R. de Costa ,  Celia Dominguez ,  Xiao-Shu He ,  Kenner C. Rice

IPC: C07D207/14 ,  C07D211/56 ,  C07D223/12 ,  C07D409/06 ,  A61K31/55 ,  A61K31/40 ,  A61K31/445 ,  C07D211/08

CPC classification number: C07D409/06 ,  C07D207/14 ,  C07D211/56 ,  C07D223/12

Abstract: Certain nitrogen-containing cyclohetero cycloalkylaminoaryl compounds are described for treatment of CNS disorders such as cerebral ischemia, psychoses and convulsions. Compounds of particular interest are of the formula: ##STR1## wherein each of R.sup.1, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 is independently selected from hydrido, lower alkyl, benzyl, and haloloweralkyl; wherein each of R.sup.2, R.sup.3 and R.sup.8 through R.sup.11 is independently selected from hydrido, hydroxy, loweralkyl, benzyl, phenoxy, benzyloxy and haloloweralkyl; wherein n is an integer of from four to six; wherein m is an integer of from two to four; wherein A is selected from phenyl, naphthyl, benzothienyl, benzofuranyl and thienyl; wherein any of the foregoing A groups can be further substituted with one or more substituents independently selected from hydrido, hydroxy, loweralkyl, loweralkoxy, halo, haloloweralkyl, amino, monoloweralkylamino and diloweralkylamino; or a pharmaceutically acceptable salt thereof.

Abstract translation: 描述某些含氮环杂环烷基氨基芳基化合物用于治疗中枢神经系统疾病如脑缺血，精神病和抽搐。 特别感兴趣的化合物具有下式：其中R 1，R 4，R 5，R 6和R 7各自独立地选自氢，低级烷基，苄基和卤代低级烷基; 其中R2，R3和R8至R11各自独立地选自氢，羟基，低级烷基，苄基，苯氧基，苄氧基和卤代低级烷基; 其中n为4-6的整数; 其中m是2至4的整数; 其中A选自苯基，萘基，苯并噻吩基，苯并呋喃基和噻吩基; 其中前述A基团中的任一个可以进一步被一个或多个独立地选自氢，羟基，低级烷基，低级烷氧基，卤素，卤代低级烷基，氨基，单低级烷基氨基和二低级烷基氨基的取代基取代。 或其药学上可接受的盐。

公开(公告)号：US09260422B2

公开(公告)日：2016-02-16

申请号：US14235253

申请日：2012-07-26

Applicant: Celia Dominguez ,  Leticia M. Toledo-Sherman ,  Stephen Martin Courtney ,  Michael Prime ,  William Mitchell ,  Christopher John Brown ,  Paula C. De Aguiar Pena ,  Peter Johnson

Inventor： Celia Dominguez ,  Leticia M. Toledo-Sherman ,  Stephen Martin Courtney ,  Michael Prime ,  William Mitchell ,  Christopher John Brown ,  Paula C. De Aguiar Pena ,  Peter Johnson

IPC: A61K31/506 ,  C07D417/04 ,  C07D239/42 ,  C07D401/04 ,  C07D403/04 ,  C07D239/26 ,  C07D413/04 ,  C07D239/28 ,  C07D413/14 ,  C07D491/044 ,  C07D491/048 ,  C07D491/052

CPC classification number: A61K31/506 ,  A61K31/505 ,  A61K31/513 ,  A61K31/5377 ,  C07D239/26 ,  C07D239/28 ,  C07D239/42 ,  C07D401/04 ,  C07D403/04 ,  C07D413/04 ,  C07D413/14 ,  C07D417/04 ,  C07D491/044 ,  C07D491/048 ,  C07D491/052

Abstract: Certain chemical entities are provided herein. Also provided are pharmaceutical compositions comprising at least one chemical entity and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described, which comprise administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one chemical entity as a single active agent or administering at least one chemical entity in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity.