公开(公告)号：US20070232617A1

公开(公告)日：2007-10-04

申请号：US11752255

申请日：2007-05-22

Applicant: Sarvajit Chakravarty ,  Sundeep Dugar ,  Qing Lu ,  Gregory Luedtke ,  Babu Mavunkel ,  John Perumattam ,  Richard Tester

Inventor： Sarvajit Chakravarty ,  Sundeep Dugar ,  Qing Lu ,  Gregory Luedtke ,  Babu Mavunkel ,  John Perumattam ,  Richard Tester

IPC: A61K31/497 ,  A61K31/445 ,  C07D401/02 ,  C07D403/02

CPC classification number: C07D401/06 ,  C07D209/18 ,  C07D209/42 ,  C07D401/14 ,  C07D403/06 ,  C07D409/12 ,  C07D409/14

Abstract: The invention is directed to methods to inhibit p38-α kinase using compounds comprising a phenyl or thienyl coupled through a piperidine or piperazine nucleus to an indole residue wherein the indole residue mandatorily has a substituent on the ring nitrogen which is an amino or substituted amino group.

Abstract translation: 本发明涉及使用包含通过哌啶或哌嗪核连接的苯基或噻吩基的化合物与吲哚残基一起抑制p38-α激酶的方法，其中吲哚残基在作为氨基或取代的氨基的环氮上强制取代基 。

公开(公告)号：US07238712B2

公开(公告)日：2007-07-03

申请号：US10156997

申请日：2002-05-28

Applicant: Babu J. Mavunkel ,  Sarvajit Chakravarty ,  John J. Perumattam ,  Sundeep Dugar ,  Qing Lu ,  Xi Liang

Inventor： Babu J. Mavunkel ,  Sarvajit Chakravarty ,  John J. Perumattam ,  Sundeep Dugar ,  Qing Lu ,  Xi Liang

IPC: A61K31/445 ,  C07D401/06

CPC classification number: C07D209/24 ,  C07D401/06 ,  C07D401/14 ,  C07D403/06 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14

Abstract: The invention is directed to methods to inhibit p38-α kinase using compounds of the formula and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein represents a single or double bond; one Z2 is CA or CR8A and the other is CR1, CR12, NR6 or N wherein each R1, R6 and R8 is independently hydrogen or noninterfering substituent; A is —Wi—COXjY wherein Y is COR2 or an isostere thereof and R2 is hydrogen or a noninterfering substituent, each of W and X is a spacer of 2–6 Å, and each of i and j is independently 0 or 1; Z3 is NR7 or O; each R3 is independently a noninterfering substituent; n is 0–3; each of L1 and L2 is a linker; each R4 is independently a noninterfering substituent; m is 0–4; Z1 is CR5 or N wherein R5 is hydrogen or a noninterfering substituent; each of l and k is an integer from 0–2 wherein the sum of l and k is 0–3; Ar is an aryl group substituted with 0–5 noninterfering substituents, wherein two noninterfering substituents can form a fused ring; and the distance between the atom of Ar linked to L2 and the center of the α ring is 4.5–24 Å.

Abstract translation: 本发明涉及使用下式的化合物及其药学上可接受的盐或其药物组合物来抑制p38-α激酶的方法，其中表示单键或双键; 一个Z 2是CA或CR 8 A，另一个是CR 1，CR 1，2， 其中每个R 1，R 6和R 8独立为氢，NR 6，N 6， 或非干扰取代基; A是其中Y是COR 2或其等同体和R 2的-Wi-i-X 氢或非干扰取代基，W和X各自为2-6的间隔基，i和j各自独立地为0或1; Z 3是NR 7或O; 每个R 3独立地是非干扰取代基; n为0-3; L 1和L 2各自为连接体; 每个R 4独立地是非干扰取代基; m为0-4; Z 1是CR 5或N，其中R 5是氢或非干扰取代基; l和k中的每一个是0-2的整数，其中l和k的和为0-3; Ar是被0-5个非直链取代基取代的芳基，其中两个非干扰取代基可以形成稠环; 并且与L 2连接的Ar原子和α环的中心之间的距离为4.5-24埃。

公开(公告)号：US07223766B2

公开(公告)日：2007-05-29

申请号：US10811428

申请日：2004-03-26

Applicant: Sundeep Dugar ,  Sarvajit Chakravarty ,  Aurelia Conte ,  Jonathan Axon ,  Glenn McEnroe ,  Alison Murphy

Inventor： Sundeep Dugar ,  Sarvajit Chakravarty ,  Aurelia Conte ,  Jonathan Axon ,  Glenn McEnroe ,  Alison Murphy

IPC: A61K31/517 ,  C07D239/70

CPC classification number: C07D487/04 ,  A61K31/517 ,  C07D239/94 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D413/14 ,  C07D471/04 ,  C07D491/04 ,  C07D493/04 ,  C07D495/04 ,  C07D498/04

Abstract: Compounds in which a pyrimidine nucleus is bridged at the 5 and 6 position and are further substituted at positions 2 and 4 with substituents comprising aromatic moieties are useful in treating subjects with rheumatoid arthritis ameliorated by inhibition of TGFβ activity.

Abstract translation: 其中嘧啶核在5和6位桥连并且在2和4位被含有芳族部分的取代基进一步取代的化合物可用于治疗通过抑制TGFbeta活性而改善的类风湿关节炎的受试者。

公开(公告)号：US07214679B2

公开(公告)日：2007-05-08

申请号：US10757023

申请日：2004-01-13

Applicant: Babu J. Mavunkel ,  Sundeep Dugar ,  Gregory R. Luedtke ,  Xuefei Tan ,  Glen McEnroe

Inventor： Babu J. Mavunkel ,  Sundeep Dugar ,  Gregory R. Luedtke ,  Xuefei Tan ,  Glen McEnroe

IPC: C07D295/03 ,  C07D403/12 ,  C07D403/14 ,  A61K31/496

CPC classification number: C07D207/416 ,  C07D211/18 ,  C07D401/06 ,  C07D471/04 ,  C07D513/04

Abstract: Compounds of the formula: wherein the substituents are as defined herein are useful for treating conditions mediated by p38 kinase.

Abstract translation: 下式的化合物：其中取代基如本文所定义，可用于治疗由p38激酶介导的病症。

公开(公告)号：US20070032506A1

公开(公告)日：2007-02-08

申请号：US11427768

申请日：2006-06-29

Applicant: Peter Giannousis ,  Kathleen Lee ,  Sundeep Dugar

Inventor： Peter Giannousis ,  Kathleen Lee ,  Sundeep Dugar

IPC: A61K31/496 ,  C07D403/02

CPC classification number: C07D209/24

Abstract: The present invention relates to novel crystalline forms of (2R-trans)-6-chloro-5-[[4-[(4-fluorophenyl)methyl]-2,5-dimethyl-1-piperazinyl]carbonyl]-N,N, 1-trimethyl-alpha-oxo-1H-indole-3-acetamide monochloride, methods for their preparation, and pharmaceutical compositions comprising the novel pseudopolymorphs.

Abstract translation: 本发明涉及（2R-反式）-6-氯-5 - [[4 - [（4-氟苯基）甲基] -2,5-二甲基-1-哌嗪基]羰基] -N，N 1-三甲基-α-氧代-1H-吲哚-3-乙酰胺一氯化物，其制备方法和包含新型假多晶型物的药物组合物。

公开(公告)号：US20050220784A1

公开(公告)日：2005-10-06

申请号：US11136242

申请日：2005-05-23

Applicant: Sarvajit Chakravarty ,  Sundeep Dugar ,  John Perumattam ,  George Schreiner ,  David Liu ,  John Lewicki

Inventor： Sarvajit Chakravarty ,  Sundeep Dugar ,  John Perumattam ,  George Schreiner ,  David Liu ,  John Lewicki

IPC: A61K31/517 ,  A61K31/519 ,  A61K31/5355 ,  A61K39/395 ,  A61P1/16 ,  A61P1/18 ,  A61P7/00 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P13/12 ,  A61P17/02 ,  A61P19/02 ,  A61P29/00 ,  A61P43/00 ,  C07D239/94 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D471/04 ,  C07D487/02

CPC classification number: C07D401/12 ,  A61K31/519 ,  C07D239/94 ,  C07D471/04

Abstract: The invention is directed to methods to inhibit TGF-β and/or p38-α kinase using compounds of the formula or the pharmaceutically acceptable salts thereof wherein R3 is a noninterfering substituent; each Z is CR2 or N, wherein no more than two Z positions in ring A are N, and wherein two adjacent Z positions in ring A cannot be N; each R2 is independently a noninterfering substituent; L is a linker; n is 0 or 1; and Ar′ is the residue of a cyclic aliphatic, cyclic heteroaliphatic, aromatic or heteroaromatic moiety optionally substituted with 1-3 noninterfering substituents.

Abstract translation: 本发明涉及使用下式的化合物或其药学上可接受的盐抑制TGF-β和/或p38-α激酶的方法，其中R 3是非干扰性取代基; 每个Z是CR 2或N，其中环A中不超过两个Z位是N，并且其中环A中的两个相邻Z位不能是N; 每个R 2独立地是非干扰取代基; L是连接体; n为0或1; 并且Ar'是任选被1-3个非干扰取代基取代的环脂族，环状杂脂族，芳族或杂芳族部分的残基。

公开(公告)号：US20050171183A1

公开(公告)日：2005-08-04

申请号：US11098905

申请日：2005-04-04

Applicant: Gregory Luedtke ,  Richland Tester ,  Sundeep Dugar ,  Qing Lu ,  John Perumattam ,  Xuefei Tan

Inventor： Gregory Luedtke ,  Richland Tester ,  Sundeep Dugar ,  Qing Lu ,  John Perumattam ,  Xuefei Tan

IPC: A61K31/404 ,  A61K31/407 ,  A61K31/454 ,  A61K31/573 ,  A61K39/395 ,  A61K45/00 ,  A61P1/04 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P17/06 ,  A61P19/02 ,  A61P19/06 ,  A61P19/08 ,  A61P25/00 ,  A61P25/08 ,  A61P25/28 ,  A61P29/00 ,  A61P31/04 ,  A61P33/06 ,  A61P35/00 ,  A61P37/06 ,  A61P43/00 ,  C07D209/18 ,  C07D401/06 ,  C07D401/12 ,  C07D403/12 ,  C07D487/04 ,  C07D487/10 ,  A61K31/405 ,  C07D487/02 ,  C07D43/02

CPC classification number: C07D401/12 ,  C07D209/18 ,  C07D403/12 ,  C07D487/04 ,  C07D487/10

Abstract: Compounds that inhibit p38-α kinase are those wherein a bicyclic aromatic system is coupled through a saturated ring to an aryl group.

Abstract translation: 抑制p38-α激酶的化合物是其中双环芳族体系通过饱和环与芳基偶联的化合物。

公开(公告)号：US06821966B2

公开(公告)日：2004-11-23

申请号：US09990187

申请日：2001-11-20

Applicant: Sundeep Dugar ,  John Perumattam ,  Gregory Luedtke ,  Xuefei Tan ,  Qing Lu

Inventor： Sundeep Dugar ,  John Perumattam ,  Gregory Luedtke ,  Xuefei Tan ,  Qing Lu

IPC: C07D40306

CPC classification number: C07D401/06 ,  C07D209/42 ,  C07D401/14 ,  C07D403/06 ,  C07D403/12 ,  C07D417/14

Abstract: The invention is directed to methods to inhibit p38-&agr; kinase using compounds of the formula and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein represents a single or double bond; B is —Wi—COXjY wherein Y is COR2 or an isostere thereof and R2 is hydrogen or a noninterfering substituent, each of W and X is a spacer of 2-6 Å, and each of i and j is independently 0 or 1; each R3 is independently a noninterfering substituent, where n is 0-3; Z3 is NR7 or O; wherein R7 is H or a noninterfering substituent; one Z2 is CA or CR8A and the other is CR1, CR12, NR6 or N wherein each R1, R6 and R8 is independently hydrogen or noninterfering substituent; wherein A is: such that Z1 is CR5 or N wherein R5 is hydrogen or a noninterfering substituent; each of l and k is an integer from 0-2 wherein the sum of l and k is 0-3; Ar is an aryl group substituted with 0-5 noninterfering substituents, wherein two noninterfering substituents can form a fused ring; each R4 is independently a noninterfering substituent where m is 0-4; each of L1 and L2 is a linker; and the distance between the atom of Ar linked to L2 and the center of the &bgr; ring is 4.5-24 Å.

Abstract translation: 本发明涉及使用下式的化合物及其药学上可接受的盐或其药物组合物抑制p38-α激酶的方法，其中表示单键或双键; B是-Wi-COXjY，其中Y是COR 2或其等同体，R 2 是氢或不干扰取代基，W和X各自为2-6的间隔基，i和j各自独立地为0或1;每个R 3独立地为非干扰取代基，其中n为0- 3; Z 3为NR 7或O; 其中R 7是H或不干扰取代基;一个Z 2是CA或CR 8，另一个是CR 1，CR 1，NR 6或N，其中每个R' R 6和R 8独立地是氢或非中间取代基; 其中A是：使得Z 1是CR 5或N，其中R 5是氢或非干扰取代基; l和k各自是0-2的整数，其中l和k的和为0 -3; Ar是被0-5个非直链取代基取代的芳基，其中两个不干扰的取代基可以形成稠环;每个R 4独立地是非干扰取代基，其中m是0-4; L 1和 L 2是连接体; 并且与L 2连接的Ar原子与β环的中心之间的距离为4.5-24埃。

公开(公告)号：US06498168B2

公开(公告)日：2002-12-24

申请号：US09902849

申请日：2001-07-11

Applicant: Derek Lowe ,  Wei Chang ,  Joseph Kozlowski ,  Joel G. Berger ,  Robert McQuade ,  Allen Barnett ,  Margaret Sherlock ,  Wing Tom ,  Sundeep Dugar ,  Lian-Yong Chen ,  John W Clader ,  Samuel Chackalamannil ,  Wang Yuguang ,  Stuart W. McCombie ,  Jayaram R. Tagat ,  Susan F. Vice ,  Wayne Vaccaro ,  Michael J. Green ,  Margaret E. Browne ,  Theodros Asberom

Inventor： Derek Lowe ,  Wei Chang ,  Joseph Kozlowski ,  Joel G. Berger ,  Robert McQuade ,  Allen Barnett ,  Margaret Sherlock ,  Wing Tom ,  Sundeep Dugar ,  Lian-Yong Chen ,  John W Clader ,  Samuel Chackalamannil ,  Wang Yuguang ,  Stuart W. McCombie ,  Jayaram R. Tagat ,  Susan F. Vice ,  Wayne Vaccaro ,  Michael J. Green ,  Margaret E. Browne ,  Theodros Asberom

IPC: C07D40102

CPC classification number: C07D211/20 ,  C07C2601/14 ,  C07D211/22 ,  C07D211/24 ,  C07D211/32 ,  C07D211/58 ,  C07D213/643 ,  C07D213/65 ,  C07D213/68 ,  C07D237/14 ,  C07D239/34 ,  C07D239/38 ,  C07D257/04 ,  C07D277/34 ,  C07D295/03 ,  C07D295/088 ,  C07D295/092 ,  C07D295/096 ,  C07D295/112 ,  C07D295/116 ,  C07D295/125 ,  C07D295/13 ,  C07D295/135 ,  C07D295/145 ,  C07D295/15 ,  C07D295/26 ,  C07D307/33 ,  C07D333/20 ,  C07D335/02 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14

Abstract: Di-N-substituted piperazine or 1,4 di-substituted piperadine compounds in accordance with formula I (including all isomers, salts, esters, and solvates) wherein R, R1, R2, R3, R4, R21, R27, R28, X, Y, and Z are as defined herein are muscarinic antagonists useful for treating cognitive disorders such as Alzheimer's disease. Pharmaceutical compositions and methods of preparation are also disclosed. Also disclosed are synergistic combinations of compounds of the above formula or other compounds capable of enhancing acetylcholine release with acetylcholinesterase inhibitors.

Abstract translation: 根据式I的二-N-取代哌嗪或1,4-二取代哌嗪化合物（包括所有异构体，盐，酯和溶剂合物），其中R，R 1，R 2，R 3，R 4，R 21，R 27，R 28，X Y和Z如本文所定义的是可用于治疗认知障碍如阿尔茨海默氏病的毒蕈碱拮抗剂。 还公开了药物组合物和制备方法。 还公开了上述化合物或能够与乙酰胆碱酯酶抑制剂一起增强乙酰胆碱释放的其它化合物的协同组合。

公开(公告)号：US6011059A

公开(公告)日：2000-01-04

申请号：US198159

申请日：1998-11-23

Applicant: Saleem Ahmad ,  Shung C. Wu ,  Karnail S. Atwal ,  Sundeep Dugar

Inventor： Saleem Ahmad ,  Shung C. Wu ,  Karnail S. Atwal ,  Sundeep Dugar

IPC: A61K31/165 ,  A61K31/34 ,  A61K31/343 ,  A61K31/352 ,  A61K31/353 ,  A61K31/357 ,  A61K31/36 ,  A61K31/38 ,  A61K31/395 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/415 ,  A61K31/42 ,  A61K31/4245 ,  A61K31/435 ,  A61K31/4402 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/4433 ,  A61K31/445 ,  A61K31/55 ,  A61P3/06 ,  A61P9/04 ,  A61P9/06 ,  A61P9/10 ,  A61P9/12 ,  A61P13/12 ,  C07C279/22 ,  C07C317/44 ,  C07D207/04 ,  C07D207/08 ,  C07D207/09 ,  C07D207/16 ,  C07D207/32 ,  C07D207/327 ,  C07D211/60 ,  C07D213/56 ,  C07D213/61 ,  C07D213/64 ,  C07D231/12 ,  C07D231/38 ,  C07D233/54 ,  C07D233/62 ,  C07D271/12 ,  C07D307/78 ,  C07D307/79 ,  C07D307/81 ,  C07D307/87 ,  C07D307/93 ,  C07D311/58 ,  C07D311/78 ,  C07D317/60 ,  C07D317/62 ,  C07D409/10 ,  C07D413/04 ,  C07D498/00 ,  C07D521/00 ,  A61K31/44 ,  C07C233/62

CPC classification number: C07D207/327 ,  C07C279/22 ,  C07D207/16 ,  C07D213/56 ,  C07D213/61 ,  C07D213/64 ,  C07D231/12 ,  C07D233/56 ,  C07D233/64 ,  C07D249/08 ,  C07D271/12 ,  C07D307/79 ,  C07D307/81 ,  C07D311/58 ,  C07D317/60 ,  C07D317/62 ,  C07D409/10 ,  C07D413/04 ,  C07C2101/02 ,  C07C2102/42

Abstract: Acyl guanidines are provided which are sodium/proton exchange (NHE) inhibitors which have the structure ##STR1## wherein n is 1 to 5; X is N or C--R.sup.5 wherein R.sup.5 is H, halo, alkenyl, alkynyl, alkoxy, alkyl, aryl or heteroaryl; and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined herein, and where X is N, R.sup.1 is preferably aryl or heteroaryl, and are useful as antianginal and cardioprotective agents. In addition, a method is provided for preventing or treating angina pectoris, cardiac dysfunction, myocardial necrosis, and arrhythmia employing the above acyl guanidines.

Abstract translation: 提供了酰基胍，其是具有其中n为1至5的结构的钠/质子交换（NHE）抑制剂; X是N或C-R5，其中R5是H，卤素，烯基，炔基，烷氧基，烷基，芳基或杂芳基; 并且R 1，R 2，R 3和R 4如本文所定义，并且其中X为N，R 1优选为芳基或杂芳基，并且可用作抗心绞痛和心脏保护剂。 此外，提供了一种用于预防或治疗心绞痛，心脏功能障碍，心肌坏死和使用上述酰基胍的心律失常的方法。