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1. 发明授权

US06589954B1 Compounds and methods to treat cardiac failure and other disorders 有权
标题翻译：治疗心力衰竭和其他疾病的化合物和方法
公开(公告)号：US06589954B1
公开(公告)日：2003-07-08
申请号：US09316761
申请日：1999-05-21
申请人： Babu J. Mavunkel , David Y. Liu , George F. Schreiner , John A. Lewicki , John J. Perumattam
发明人： Babu J. Mavunkel , David Y. Liu , George F. Schreiner , John A. Lewicki , John J. Perumattam
IPC分类号： A61K31495
CPC分类号： C07D401/06 , C07D209/08 , C07D209/24 , C07D235/06 , C07D401/14 , C07D403/06 , C07D471/04
摘要： Indoles, benzimidazoles and benztriazoles which are substituted at the 5 or 6 position with a substituent comprising an aromatic moiety linked through a piperazine ring to said indole, benzimidazole or benztriazole are useful in treating cardiac conditions associated with heart failure and in treating conditions characterized by proinflammation.
摘要翻译：在5或6位被取代基的吲哚，苯并咪唑和苯并三唑与包含通过哌嗪环连接到所述吲哚，苯并咪唑或苯并三唑的芳族部分的取代基可用于治疗与心力衰竭相关的心脏病症和治疗以促炎症为特征的病症。

2. 发明授权

US06541477B2 Inhibitors of p38-a kinase 有权
标题翻译： p38-a激酶抑制剂
公开(公告)号：US06541477B2
公开(公告)日：2003-04-01
申请号：US09796997
申请日：2001-02-28
申请人： R. Richard Goehring , Babu J. Mavunkel , David Y. Liu , George F. Schreiner , Gregory Leudtke , John A. Lewicki
发明人： R. Richard Goehring , Babu J. Mavunkel , David Y. Liu , George F. Schreiner , Gregory Leudtke , John A. Lewicki
IPC分类号： A61K31495
CPC分类号： C07D215/04 , A61K31/00 , A61K31/426 , A61K31/445 , A61K31/4535 , A61K31/454 , A61K31/4545 , A61K31/4709 , A61K31/495 , A61K31/496 , A61K31/522 , A61K31/5377 , A61K45/06 , C07D209/08 , C07D211/14 , C07D211/16 , C07D215/06 , C07D235/06 , C07D277/52 , C07D295/192 , C07D307/68 , C07D401/04 , C07D401/06 , C07D401/10 , C07D401/12 , C07D401/14 , C07D405/12 , C07D409/06 , C07D471/04 , C07D471/10 , C07D473/06 , C07D495/04
摘要： The invention is directed to methods for treating conditions mediated by by P38&agr; kinase using compounds of the formula wherein Ar1 and Ph are limited to specific embodiments or wherein the compound of formula (3) is a compound set forth in FIGS. 1A-1T.
摘要翻译：本发明涉及用于治疗由P38α激酶介导的病症的方法，其中使用化学式Ar1和Ph的化合物限于具体实施方案或其中式（3）化合物是图1和图2所示的化合物。 1A-1T。

3. 发明授权

US07189739B2 Compounds and methods to treat cardiac failure and other disorders 有权
标题翻译：治疗心力衰竭和其他疾病的化合物和方法
公开(公告)号：US07189739B2
公开(公告)日：2007-03-13
申请号：US10076131
申请日：2002-02-13
申请人： Babu J. Mavunkel , David Y. Liu , George F. Schreiner , John A. Lewicki , John J. Perumattam
发明人： Babu J. Mavunkel , David Y. Liu , George F. Schreiner , John A. Lewicki , John J. Perumattam
IPC分类号： A61K31/445 , C07D401/06
CPC分类号： C07D401/06 , C07D209/08 , C07D209/24 , C07D235/06 , C07D401/14 , C07D403/06 , C07D471/04
摘要： The invention is directed to compounds of the formula and the pharmaceutically acceptable salts thereof wherein Ar1 is indole, benzimidazole, or benzotriazole, optionally substituted with lower alkyl (1–4C), halo, or lower alkoxy (1–4C); X1 is CO or an isostere thereof; Y is optionally substituted alkyl, optionally substituted aryl, or optionally substituted arylalkyl; n is 0 or 1; Z is CH or N; X2 is CH, CH2 or an isostere thereof; and Ar2 consists of one or two phenyl moieties directly coupled to X2 and optionally substituted by halo, nitro, alkyl (1–6C), CN or CF3, or by RCO, COOR, CONR2, NR2, OR or SR, wherein R is H or alkyl (1–6C) or by phenyl, itself optionally substituted by the foregoing substituents; with the proviso that if Z is N, X1 is CO, and Ar1 is indole, Ar1 must be coupled to X1 through the 2-, 5-, 6- or 7-position. These compounds are useful in the treatment of conditions associated with inflammation. In addition, the above compounds and other compounds described herein are useful in treating conditions associated with cardiac failure.
摘要翻译：本发明涉及下式的化合物及其药学上可接受的盐，其中Ar 1是吲哚，苯并咪唑或苯并三唑，任选被低级烷基（1-4C），卤素或低级烷氧基（ 1-4C）; X 1是CO或其等同体; Y是任选取代的烷基，任选取代的芳基或任选取代的芳基烷基; n为0或1; Z是CH或N; X 2是CH，CH 2或它们的等离子体; 和Ar 2由一个或两个直接与X 2连接的苯基部分组成，并且任选被卤素，硝基，烷基（1-6C），CN或CF 3或RCO，COOR，CONR 2，NR 2，OR或SR，其中R是H或烷基（1-6C）或苯基本身任选被上述取代基取代; 条件是如果Z为N，则X 1为CO，Ar 1为吲哚，则Ar 1必须与X ^{1 通过2-，5-，6-或7-位。这些化合物可用于治疗与炎症相关的病症。此外，本文所述的上述化合物和其它化合物可用于治疗与心力衰竭相关的病症。}

4. 发明授权

US06340685B1 Compounds and methods to treat cardiac failure and other disorders 有权
标题翻译：治疗心力衰竭和其他疾病的化合物和方法
公开(公告)号：US06340685B1
公开(公告)日：2002-01-22
申请号：US09275176
申请日：1999-03-24
申请人： Babu J. Mavunkel , John A. Lewicki , David Y. Liu , George F. Schreiner , John J. Perumattam
发明人： Babu J. Mavunkel , John A. Lewicki , David Y. Liu , George F. Schreiner , John J. Perumattam
IPC分类号： A61K31496
CPC分类号： C07D235/06 , C07D209/08 , C07D401/06 , C07D401/14 , C07D403/06
摘要： A compound of the formula: and the pharmaceutically acceptable salts thereof, wherein each of Z1 and Z2 is independently CR4 or N; where each R4 is independently H or is alkyl (1-6C) optionally including one or more heteroatoms selected from O, S and N and optionally substituted by one or more of halo, OR, SR, NR2, RCO, COOR, CONR2, OOCR, or NROCR where R is H or alkyl (1-6C), or by CN or ═O, or by an aliphatic or aromatic 5 or 6 membered ring optionally containing 1-2 N heteroatoms; or two R4 taken together form a bridge optionally containing a heteroatom; R1 is wherein X1 is CO or an isostere thereof; m is 0 or 1; Y is optionally substituted alkyl, optionally substituted aryl, or optionally substituted arylalkyl or two 6 taken together may form an alkyene (2-3C) bridge; n is 0 or 2; Z3 is CH or N; X2 is CH, CH2 or an isostere thereof; and Ar consists of one or two phenyl moieties directly coupled to X2 optionally substituted by halo, nitro, alkyl (1-6C), alkenyl (1-6C), CN or CF3, or by RCO, COOR, CONR2, NR2, OR, SR, OOCR or NROCR wherein R is H or alkyl (1-6C) or by phenyl, itself optionally substituted by the foregoing substituents; R2 is H, or alkyl (1-6C) optionally including one heteroatom which is O, S or N, and optionally substituted by one or more of halo, OR, SR, NR2, RCO, COOR, CONR2, OOCR, or NROCR where R is H or alkyl (1-6C), or by CN or ═O, or by an aliphatic or aromatic 5 or 6 membered ring optionally containing 1-2 N heteroatoms; R3 is H, halo, NO2, alkyl (1-6C), alkenyl (1-6C), CN, OR, SR, NR2, RCO, COOR, CONR2, OOCR, or NROCR where R is H or alkyl (1-6C).
摘要翻译：下式化合物及其药学上可接受的盐，其中Z 1和Z 2各自独立地为CR 4或N;其中每个R 4独立地为H或烷基（1-6C），任选地包括一个或多个选自O，S 其中R是H或烷基（1-6C），或CN或= O，或被一个或多个选自下列基团取代：卤素，OR，SR，NR2，RCO，COOR，CONR2，OOCR或NROCR，任选含有1-2个N杂原子的脂族或芳族5或6元环; R 2一起形成任选含有杂原子的桥; R 1是其中X 1是CO或其等同体; m是0或1; Y是任选取代的烷基，任选取代的芳基或任选取代的芳烷基或两个6一起形成烷基（2-3C）桥; n为0或2; Z3为CH或N; X2为CH，CH2或其等同基团; 并且Ar由直接连接到X2上的一个或两个苯基部分，任选被卤素，硝基，烷基（1-6C），烯基（1-6C），CN或CF 3或RCO，COOR，CONR2，NR2，OR，SR ，OOCR或NROCR，其中R为H或烷基（1-6C）或苯基，其本身任选被前述取代基取代; R 2为H或任选包括一个为O，S或N的杂原子的烷基（1-6C）并且任选被一个或多个卤素，OR，SR，NR 2，RCO，COOR，CONR 2，OOCR或NROCR取代，其中R是H或烷基（1-6C），或CN或= O，或被脂族或芳香族5或6元环，任选地含有1-2个N杂原子; R3是H，卤素，NO2，烷基（1-6C），烯基（1-6C），CN，OR，SR，NR2，RCO，COOR，CONR2， OOCR或NROCR，其中R是H或烷基（1-6C）。

5. 发明授权

US06448257B1 Compounds and methods to treat cardiac failure and other disorders 有权
标题翻译：治疗心力衰竭和其他疾病的化合物和方法
公开(公告)号：US06448257B1
公开(公告)日：2002-09-10
申请号：US09535316
申请日：2000-03-24
申请人： Babu J. Mavunkel , David Y. Liu , George F. Schreiner , John A. Lewicki
发明人： Babu J. Mavunkel , David Y. Liu , George F. Schreiner , John A. Lewicki
IPC分类号： A61K31437
CPC分类号： C07D209/08 , C07D209/24 , C07D235/06 , C07D401/06 , C07D401/14 , C07D403/06 , C07D471/04
摘要： Compounds of the formula: wherein the dotted line represents an optional bond; and the pharmaceutically acceptable salts thereof, wherein X1 is an alkyl bridge optionally containing an O, S, or N heteroatom that forms an aliphatic 5-7 membered ring and is optionally substituted by one or more of halo, OR, SR, NR2, RCO, COOR, CONR2, OOCR, or NROCR where R is H or alkyl (1-6C), or by one or more CN or═O, or by one or more aliphatic or aromatic 5- or 6-membered rings optionally containing 1-2 heteroatoms; R1 is wherein X2 is CO or an isostere thereof; m is 0 or 1; Y is optionally substituted alkyl, optionally substituted aryl, or optionally substituted arylalkyl or two Y taken together may form an alkylene (2-3C) bridge; n is 0-4; Z1 is CH or N; X3 is CH or CHR where R is H or alkyl (1-6C), or an isostere thereof; and Ar, R2 and R3 are as defined in the specification. These compounds are selective inhibitors of p38&agr; kinase.
摘要翻译：下式的化合物：其中虚线表示任选的键;及其药学上可接受的盐，其中X 1是任选地含有O，S或N杂原子的烷基桥，其形成脂族5-7元环并任选被取代其中R是H或烷基（1-6C），或一个或多个CN或= O，或一个或多个卤素，OR，SR，NR 2，RCO，COOR，CONR 2，OOCR或NROCR 任选含有1-2个杂原子的脂族或芳族五元或六元环; R 1是其中X 2是CO或其等价物; m是0或1; Y是任选取代的烷基，任选取代的芳基或任选取代的芳基烷基或两个Y 一起可以形成亚烷基（2-3C）桥; n为0-4; Z1为CH或N; X3为CH或CHR，其中R为H或烷基（1-6C）或其等同体; 并且Ar，R 2和R 3如本说明书中所定义。这些化合物是p38alpha激酶的选择性抑制剂。

6. 发明授权

US06410540B1 Inhibitors of p38-&agr;kinase 有权
标题翻译： p38-alphakinase的抑制剂
公开(公告)号：US06410540B1
公开(公告)日：2002-06-25
申请号：US09385494
申请日：1999-08-27
申请人： R. Richard Goehring , Gregory R. Luedtke , Babu J. Mavunkel , Sarvajit Chakravarty , Sundeep Dugar , George F. Schreiner , David Y. Liu , John A. Lewicki
发明人： R. Richard Goehring , Gregory R. Luedtke , Babu J. Mavunkel , Sarvajit Chakravarty , Sundeep Dugar , George F. Schreiner , David Y. Liu , John A. Lewicki
IPC分类号： A61K3150
CPC分类号： A61K45/06 , A61K31/00 , A61K31/426 , A61K31/4365 , A61K31/437 , A61K31/445 , A61K31/4535 , A61K31/454 , A61K31/4545 , A61K31/4709 , A61K31/4725 , A61K31/495 , A61K31/496 , A61K31/4965 , A61K31/497 , A61K31/506 , A61K31/519 , A61K31/522 , Y02A50/411
摘要： The invention is directed to methods to treat conditions mediated by p38-&agr;kinase using compounds of the formula and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein Z is N or CR1, R1 is a noninterfering substituent, each of X1 and X2 is a linker, Ar1 and Ar2 are identical or different, and represent optionally substituted C1-C20 hydrocarbyl residues wherein at least one of Ar1 and Ar2 is an optionally substituted aryl group, with the proviso that when X2 is CH2 or an isostere thereof, X1 is CO or an isostere thereof, and Ar2 is optionally substituted phenyl, Ar1 is other than an optionally substituted indolyl, benzimidazolyl or benzotriazolyl substituent, and wherein said optionally substituted phenyl is not an optionally substituted indolyl, benzimidazolyl, or benzotriazolyl, Y is a noninterfering substituent, wherein n is an integer from 0-4, and wherein m is an integer from 0-4 and 1 is an integer from 0-3.
摘要翻译：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治疗由p38-阿拉蛋白酶介导的病症的方法，其中Z是N或CR1，R1是不干扰取代基，X1和X2分别是连接基，Ar 1和Ar 2相同或不同，并且表示任选取代的C 1 -C 20烃基残基，其中Ar 1和Ar 2中的至少一个是任选取代的芳基，条件是当X 2是CH 2或其等同体时，X 1是CO 或其等同物，Ar 2是任选取代的苯基，Ar 1不同于任选取代的吲哚基，苯并咪唑基或苯并三唑基取代基，并且其中所述任选取代的苯基不是任选取代的吲哚基，苯并咪唑基或苯并三唑基，Y是非干扰取代基，其中n是0-4的整数，其中m是0-4的整数，1是0-3的整数。

7. 发明授权

US06130235A Compounds and methods to treat cardiac failure and other disorders 有权
标题翻译：治疗心力衰竭和其他疾病的化合物和方法
公开(公告)号：US06130235A
公开(公告)日：2000-10-10
申请号：US128137
申请日：1998-08-03
申请人： Babu J. Mavunkel , John A. Lewicki , David Y. Liu , George F. Schreiner
发明人： Babu J. Mavunkel , John A. Lewicki , David Y. Liu , George F. Schreiner
IPC分类号： C07D209/08 , C07D235/06 , C07D401/06 , C07D401/14 , C07D403/06 , A61K31/445
CPC分类号： C07D209/08 , C07D235/06 , C07D401/06 , C07D401/14 , C07D403/06
摘要： The invention is directed to compounds of the formula ##STR1## and the pharmaceutically acceptable salts thereof wherein Ar.sup.1 is indole, benzimidazole, or benzotriazole, optionally substituted with lower alkyl (1-4C), halo, or lower alkoxy (1-4C);X.sup.1 is CO or an isostere thereof;Y is optionally substituted alkyl, optionally substituted aryl, or optionally substituted arylalkyl;n is 0 or 1;Z is CH or N;X.sup.2 is CH, CH.sub.2 or an isostere thereof; andAr.sup.2 consists of one or two phenyl moieties directly coupled to X.sup.2 and optionally substituted by halo, nitro, alkyl (1-6C), CN or CF.sub.3, or by RCO, COOR, CONR.sub.2, NR.sub.2, OR or SR, wherein R is H or alkyl (1-6C) or by phenyl, itself optionally substituted by the foregoing substituents;with the proviso that if Z is N, X.sup.1 is CO, and Ar.sup.1 is indole, Ar.sup.1 must be coupled to X.sup.1 through the 2-, 5-, 6- or 7-position.These compounds are useful in the treatment of conditions associated with inflammation. In addition, the above compounds and other compounds described herein are useful in treating conditions associated with cardiac failure.
摘要翻译：本发明涉及下式的化合物及其药学上可接受的盐，其中Ar 1是任选被低级烷基（1-4C），卤素或低级烷氧基（1-4C）取代的吲哚，苯并咪唑或苯并三唑; X1是CO或其等离子体; Y是任选取代的烷基，任选取代的芳基或任选取代的芳基烷基; n为0或1; Z是CH或N; X 2是CH，CH 2或其等价物; 并且Ar 2由直接与X 2连接并任选被卤素，硝基，烷基（1-6C），CN或CF 3或RCO，COOR，CONR2，NR2，OR或SR取代的一个或两个苯基部分组成，其中R为H 或烷基（1-6C）或苯基，其本身任选被上述取代基取代; 条件是如果Z是N，则X1是CO，Ar1是吲哚，Ar1必须通过2-，5-，6-或7-位与X1连接。这些化合物可用于治疗与炎症相关的病症。此外，本文所述的上述化合物和其它化合物可用于治疗与心力衰竭相关的病症。

8. 发明授权

US06903096B2 Quinazoline derivatives as medicaments 有权
公开(公告)号：US06903096B2
公开(公告)日：2005-06-07
申请号：US09972582
申请日：2001-10-05
申请人： Sarvajit Chakravarty , Sundeep Dugar , John J. Perumattam , George F. Schreiner , David Y. Liu , John A. Lewicki
发明人： Sarvajit Chakravarty , Sundeep Dugar , John J. Perumattam , George F. Schreiner , David Y. Liu , John A. Lewicki
IPC分类号： 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分类号： C07D401/12 , A61K31/519 , C07D239/94 , C07D471/04
摘要： 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.

9. 发明授权

US06277989B1 Quinazoline derivatives as medicaments 有权
标题翻译：喹唑啉衍生物作为药物
公开(公告)号：US06277989B1
公开(公告)日：2001-08-21
申请号：US09525034
申请日：2000-03-14
申请人： Sarvajit Chakravarty , Sundeep Dugar , John J. Perumattam , George F. Schreiner , David Y. Liu , John A. Lewicki
发明人： Sarvajit Chakravarty , Sundeep Dugar , John J. Perumattam , George F. Schreiner , David Y. Liu , John A. Lewicki
IPC分类号： C07D23942
CPC分类号： C07D401/12 , A61K31/519 , C07D239/94 , C07D471/04
摘要： The invention is directed to methods to inhibit TGF-&bgr; and/or p38-&agr; 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.
摘要翻译：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R3是不干扰取代基;每个Z是CR2或N，其中环中不超过两个Z位置 A是N，并且其中环A中的两个相邻Z位不能是N;每个R2独立地是非干扰取代基; L是连接基; n是0或1; 并且Ar'是任选被1-3个非干扰取代基取代的环状脂族，环状杂脂族，芳族或杂芳族部分的残基。

10. 发明授权

US06184226B2 Quinazoline derivatives as inhibitors of P-38 &agr; 有权
标题翻译：喹唑啉衍生物作为P-38α的抑制剂
公开(公告)号：US06184226B2
公开(公告)日：2001-02-06
申请号：US09141916
申请日：1998-08-28
申请人： Sarvajit Chakravarty , John J. Perumattam , George F. Schreiner , David Y. Liu , John A. Lewicki
发明人： Sarvajit Chakravarty , John J. Perumattam , George F. Schreiner , David Y. Liu , John A. Lewicki
IPC分类号： A01N5500
CPC分类号： C07D401/12 , A61K31/519 , C07D239/94 , C07D471/04
摘要： The invention describes compounds of the formula and the pharmaceutically acceptable salts thereof and the pharmaceutically acceptable salts thereof wherein each R2 is independently a noninterfering substituent; m is an integer of 0-4; Z is CH or N; R1 is H, alkyl (1-6C) or arylalkyl optionally substituted on the aryl group with 1-3 substituents independently selected from alkyl (1-6C), halo, OR, NR2, SR, —OOCR, —NROCR, RCO, —COOR, —CONR2, —SO2NR2, CN, CF3, and NO2, wherein each R is independently H or lower alkyl (1-4C); n is 0, 1 or 2; Ar is phenyl, pyridyl, indolyl, or pyrimidyl, each optionally substituted with a group selected from the group consisting of optionally substituted alkyl (1-6C), halo, OR, NR2, SR, —OOCR, —NROCR, RCO, —COOR, —CONR2, SO2NR2, CN, CF3, and NO2, wherein each R is independently H or lower alkyl (1-4C); and R3 is a branched or cyclic alkyl group (5-7C) or is phenyl optionally substituted with 1-2 substituents which substituents are selected from the group consisting of alkyl (1-6C), halo, OR, NR2, SR, —OOCR, —NROCR, RCO, —COOR, —CONR2, —SO2NR2, CN, CF3, and NO2, wherein each R is independently H or lower alkyl (1-4C) which are useful as antiinflammatories and in treating cardiac disorders.
摘要翻译：本发明描述了下式的化合物及其药学上可接受的盐及其药学上可接受的盐，其中R2各自独立地为非干扰性取代基; m为0-4的整数; Z为CH或N; R 1为H，烷基（1-6C）（1-6C），卤素，OR，NR2，SR，-OOCR，-NROCR，RCO，-COOR，-CONR2，-SO2NR2，CN等的任选取代的芳基， CF 3和NO 2，其中每个R独立地为H或低级烷基（1-4C）; n为0,1或2; Ar为苯基，吡啶基，吲哚基或嘧啶基，各自任选被选自以下的基团取代：任选取代的烷基（1-6C），卤素，OR，NR2，SR，-OOCR，-NROCR，RCO，-COOR，-CONR2，SO2NR2，CN，CF3和NO2，其中每个R独立地为H或低级烷基（1-4C）; 和R 3是支链或环状烷基（5-7C），或是任选被1-2个取代基取代的苯基，所述取代基选自烷基（1-6C），卤素，OR，NR2，SR，-OOCR， -NROCR，RCO，-COOR，-CONR2，-SO2NR2，CN，CF3和NO2，其中每个R独立地为H或可用作抗炎剂和治疗心脏疾病的低级烷基（1-4C）。

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