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1. 发明申请

WO9816503A2 THE PREPARATION AND USE OF ORTHO-SULFONAMIDO ARYL HYDROXAMIC ACIDS AS MATRIX METALLOPROTEINASE AND TACE INHIBITORS 审中-公开
标题翻译： ORTHO-SULFONAMIDO ARYL HYDROXAMICIC作为基质金属蛋白酶和TACE抑制剂的制备和使用
公开(公告)号：WO9816503A2
公开(公告)日：1998-04-23
申请号：PCT/US9718280
申请日：1997-10-08
申请人： AMERICAN CYANAMID CO
发明人： LEVIN JEREMY IAN , DU MILA T , VENKATESAN ARANAPAKAM MUDUMBAI , NELSON FRANCES CHRISTY , ZASK ARIE , GU YANSONG
IPC分类号： C07D295/12 , A61K31/18 , A61K31/216 , A61K31/381 , A61K31/422 , A61K31/4406 , A61K31/443 , A61K31/4433 , A61K31/4436 , A61K31/495 , A61K31/496 , A61K31/5377 , A61K31/553 , A61K31/695 , A61P1/02 , A61P1/04 , A61P9/10 , A61P13/02 , A61P13/12 , A61P17/00 , A61P19/04 , A61P25/28 , A61P27/02 , A61P29/00 , A61P31/18 , A61P35/04 , A61P37/00 , A61P43/00 , C07C311/21 , C07C311/29 , C07D213/42 , C07D213/68 , C07D267/02 , C07D267/14 , C07D267/20 , C07D273/06 , C07D333/20 , C07D333/24 , C07D401/12 , C07D405/12 , C07D409/04 , C07D409/12 , C07D413/04 , C07D413/12 , C07D413/14 , C07F7/18 , C07C311/00
CPC分类号： C07D213/42 , C07C311/21 , C07C311/29 , C07D213/68 , C07D267/14 , C07D273/06 , C07D333/20 , C07D401/12 , C07D405/12 , C07D409/04 , C07D409/12 , C07D413/14 , C07F7/1852
摘要： The present invention relates to the discovery of novel, low molecular weight, non-peptide inhibitors of matrix metalloproteinases (e.g. gelatinases, stromelysins and collagenases) and TNF- alpha converting enzyme (TACE, tumor necrosis factor- alpha converting enzyme) which are useful for the treatment of diseases in which these enzymes are implicated such as arthritis, tumor growth and metastasis, angiogenesis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, proteinuria, aneurysmal aortic disease, degenerative cartilage loss following traumatic joint injury, demyelinating diseases of the nervous system, graft rejection, cachexia, anorexia, inflammation, fever, insulin resistance, septic shock, congestive heart failure, inflammatory disease of the central nervous system, inflammatory bowel disease, HIV infection, age related macular degeneration, diabetic retinopathy, proliferative vitreoretinopathy, retinopathy of prematurity, ocular inflammation, keratoconus, Sjogren's syndrome, myopia, ocular tumors, ocular angiogenesis/neovascularization. The TACE and MMP inhibiting ortho-sulfonamido aryl hydroxamic acids of the present invention are represented by formula (I) where the hydroxamic acid moiety and the sulfonamido moiety are bonded to adjacent carbons on group A where: A is phenyl or naphthyl, optionally substituted by R , R , R and R ; Z is aryl, heteroaryl, or heteroaryl fused to a phenyl, where aryl is phenyl or naphthyl optionally substituted by R , R , R and R ; heteroaryl is a 5-6 membered heteroaromatic ring having from 1 to 3 heteroatoms independently selected from N, O and S, and optionally substituted by R , R , R and R ; and when heteroaryl is fused to phenyl, either or both of the rings can be optionally substituted by R , R , R and R ; and R , R , R , R , R , R , R , R and R are described in the specification, and the pharmaceutically acceptable salts thereof and the optical isomers and diastereomers thereof.
摘要翻译：本发明涉及基因金属蛋白酶（例如明胶酶，基质溶质蛋白和胶原酶）和TNF-α转化酶（TACE，肿瘤坏死因子-α转化酶）的新型低分子量非肽抑制剂的发现，其可用于这些酶涉及的疾病如关节炎，肿瘤生长和转移，血管生成，组织溃疡，伤口愈合异常，牙周病，骨病，蛋白尿，动脉瘤主动脉疾病，创伤性关节损伤后退行性软骨损失，脱髓鞘疾病的神经系统，移植排斥反应，恶病质，厌食，炎症，发烧，胰岛素抵抗，脓毒性休克，充血性心力衰竭，中枢神经系统炎性疾病，炎症性肠病，HIV感染，年龄相关性黄斑变性，糖尿病性视网膜病变，增殖性玻璃体视网膜病变，早产儿视网膜病变，眼部炎症，角蛋白职业，干燥综合征，近视眼眼肿瘤，眼血管生成/新生血管形成。本发明的TACE和MMP抑制邻氨基磺酰氨基芳基异羟肟酸由式（I）表示，其中异羟肟酸部分和亚磺酰氨基部分与A组相邻的碳键合，其中：A是苯基或萘基，任选被 R 1，R 2，R 3和R 4; Z是芳基，杂芳基或与苯基稠合的杂芳基，其中芳基是任选被R 1，R 2，R 3和R 4取代的苯基或萘基; 杂芳基是具有1至3个独立地选自N，O和S的杂原子并且任选被R 1，R 2，R 3和R 4取代的5-6元杂芳环; 当杂芳基与苯基稠合时，任一个或两个环可任选被R 1，R 2，R 3和R 4取代; 在本说明书中描述了R 1，R 2，R 3，R 4，R 5，R 6，R 7，R 8和R 9 及其药学上可接受的盐及其旋光异构体和非对映异构体。

2. 发明专利

EE04295B1 未知
公开(公告)号：EE04295B1
公开(公告)日：2004-06-15
申请号：EEP9900371
申请日：1998-02-17
申请人： AMERICAN CYANAMID CO
发明人： VENKATESAN ARANAPAKAM MUDUMBAI , GROSU GEORGE THEODORE , DAVIS JAMIE MARIE , BAKER JANNIE LEA
IPC分类号： C07D295/08 , A61K31/16 , A61K31/165 , A61K31/341 , A61K31/351 , A61K31/381 , A61K31/40 , A61K31/4035 , A61K31/41 , A61K31/415 , A61K31/4164 , A61K31/4166 , A61K31/4184 , A61K31/423 , A61K31/426 , A61K31/428 , A61K31/433 , A61K31/4402 , A61K31/4406 , A61K31/4409 , A61K31/4436 , A61K31/445 , A61K31/4453 , A61K31/4535 , A61K31/47 , A61K31/495 , A61K31/4965 , A61K31/5375 , A61K31/55 , A61P1/02 , A61P1/04 , A61P1/14 , A61P3/10 , A61P9/02 , A61P9/04 , A61P17/02 , A61P19/02 , A61P19/08 , A61P29/00 , A61P31/18 , A61P35/00 , A61P35/04 , A61P37/06 , C07C317/40 , C07C317/44 , C07C317/46 , C07C323/60 , C07D207/12 , C07D209/48 , C07D211/54 , C07D211/66 , C07D213/30 , C07D213/32 , C07D213/54 , C07D213/56 , C07D213/70 , C07D213/71 , C07D213/74 , C07D213/89 , C07D215/12 , C07D215/36 , C07D215/38 , C07D215/48 , C07D231/18 , C07D233/02 , C07D233/54 , C07D233/64 , C07D233/76 , C07D233/84 , C07D235/28 , C07D241/12 , C07D257/04 , C07D263/58 , C07D277/20 , C07D277/36 , C07D277/70 , C07D277/74 , C07D277/76 , C07D285/14 , C07D295/092 , C07D307/30 , C07D307/38 , C07D307/64 , C07D309/12 , C07D333/28 , C07D333/34 , C07D409/04
摘要： Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF- alpha converting enzymes (TACE), a pro-inflammatory cytokine, catalyze the formation of TNF- alpha from membrane-bound TNF- alpha precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF- alpha converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection. The compounds of this invention are represented by formula (I), where R , R , R and R are described herein.

3. 发明专利

NO314258B1 未知
公开(公告)号：NO314258B1
公开(公告)日：2003-02-24
申请号：NO994124
申请日：1999-08-26
申请人： AMERICAN CYANAMID CO
发明人： VENKATESAN ARANAPAKAM MUDUMBAI , GROSU GEORGE THEODORE , DAVIS JAMIE MARIE , HU BAIHUA , O'DELL MATHEW JAMES , COLE DEREK CECIL , BAKER JANNIE LEA , JACOBSON MARCY PAMELA
IPC分类号： C07D295/08 , A61K31/16 , A61K31/165 , A61K31/341 , A61K31/351 , A61K31/381 , A61K31/40 , A61K31/4035 , A61K31/41 , A61K31/415 , A61K31/4164 , A61K31/4166 , A61K31/4184 , A61K31/423 , A61K31/426 , A61K31/428 , A61K31/433 , A61K31/4402 , A61K31/4406 , A61K31/4409 , A61K31/4436 , A61K31/445 , A61K31/4453 , A61K31/4535 , A61K31/47 , A61K31/495 , A61K31/4965 , A61K31/5375 , A61K31/55 , A61P1/02 , A61P1/04 , A61P1/14 , A61P3/10 , A61P9/02 , A61P9/04 , A61P17/02 , A61P19/02 , A61P19/08 , A61P29/00 , A61P31/18 , A61P35/00 , A61P35/04 , A61P37/06 , C07C317/40 , C07C317/44 , C07C317/46 , C07C323/60 , C07D207/12 , C07D209/48 , C07D211/54 , C07D211/66 , C07D213/30 , C07D213/32 , C07D213/54 , C07D213/56 , C07D213/70 , C07D213/71 , C07D213/74 , C07D213/89 , C07D215/12 , C07D215/36 , C07D215/38 , C07D215/48 , C07D231/18 , C07D233/02 , C07D233/54 , C07D233/64 , C07D233/76 , C07D233/84 , C07D235/28 , C07D241/12 , C07D257/04 , C07D263/58 , C07D277/20 , C07D277/36 , C07D277/70 , C07D277/74 , C07D277/76 , C07D285/14 , C07D295/092 , C07D307/30 , C07D307/38 , C07D307/64 , C07D309/12 , C07D333/28 , C07D333/34 , C07D409/04
摘要： Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF- alpha converting enzymes (TACE), a pro-inflammatory cytokine, catalyze the formation of TNF- alpha from membrane-bound TNF- alpha precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF- alpha converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection. The compounds of this invention are represented by formula (I), where R , R , R and R are described herein.

4. 发明专利

PT805813E 未知
公开(公告)号：PT805813E
公开(公告)日：2002-10-31
申请号：PT96902143
申请日：1996-01-16
申请人： AMERICAN CYANAMID CO
发明人： ALBRIGHT JAY DONALD , VENKATESAN ARANAPAKAM MUDUMBAI , GROSU GEORGE THEODORE
IPC分类号： A61K31/495 , A61K31/55 , A61P1/16 , A61P11/00 , A61P13/02 , A61P15/00 , C07D487/04 , C07D491/14 , C07D487/14 , C07D495/14 , C07D471/14 , C07D498/14 , C07D513/14
摘要： Tricyclic diazepines of the Formula I: Formula I wherein A, B, D, E, F, Y, and Z are defined in the specification which compounds have vasopressin and oxytocin antagonist activity.

5. 发明专利

PL349042A1 ALKYNYL CONTAINING HYDROXAMIC ACID COMPOUNDS AS TACE INHIBITORS 未知
公开(公告)号：PL349042A1
公开(公告)日：2002-07-01
申请号：PL34904200
申请日：2000-01-27
申请人： AMERICAN CYANAMID CO
发明人： LEVIN JEREMY IAN , VENKATESAN ARANAPAKAM MUDUMBAI , COLE DEREK CECIL , CHEN JAMES MING , DAVIS JAMIE MARIE , GROSU GEORGE THEODORE
IPC分类号： C07D295/08 , A61K31/16 , A61K31/351 , A61K31/352 , A61K31/381 , A61K31/382 , A61K31/40 , A61K31/4035 , A61K31/4045 , A61K31/4406 , A61K31/445 , A61K31/4453 , A61K31/4465 , A61K31/47 , A61K31/472 , A61P1/04 , A61P9/04 , A61P19/02 , A61P29/00 , A61P31/18 , A61P37/00 , A61P43/00 , C07C259/06 , C07C259/10 , C07C315/04 , C07C317/22 , C07C317/44 , C07C319/20 , C07C323/20 , C07C323/60 , C07D207/34 , C07D209/14 , C07D209/18 , C07D209/48 , C07D211/34 , C07D213/56 , C07D213/82 , C07D215/16 , C07D215/48 , C07D215/54 , C07D217/06 , C07D217/26 , C07D295/092 , C07D309/04 , C07D309/10 , C07D311/84 , C07D333/20 , C07D333/24 , C07D333/58 , C07D333/60 , C07D335/02 , C07D335/04 , C07F9/53
摘要： The invention concerns compounds of formula (I) which are useful in treating disease conditions mediated by TNF- alpha , such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease and degenerative cartilage loss.

6. 发明专利

AT217625T 未知
公开(公告)号：AT217625T
公开(公告)日：2002-06-15
申请号：AT96902143
申请日：1996-01-16
申请人： AMERICAN CYANAMID CO
发明人： VENKATESAN ARANAPAKAM MUDUMBAI , ALBRIGHT JAY DONALD , GROSU GEORGE THEODORE
IPC分类号： A61K31/495 , A61K31/55 , A61P1/16 , A61P11/00 , A61P13/02 , A61P15/00 , C07D487/04 , C07D491/14 , C07D487/14 , C07D495/14 , C07D471/14 , C07D498/14
摘要： Tricyclic diazepines of the Formula I: Formula I wherein A, B, D, E, F, Y, and Z are defined in the specification which compounds have vasopressin and oxytocin antagonist activity.

7. 发明专利

CZ20012707A3 Hydroxamic acid derivatives containing alkynyl group and functioning as TACE inhibitors 未知
公开(公告)号：CZ20012707A3
公开(公告)日：2002-05-15
申请号：CZ20012707
申请日：2000-01-27
申请人： AMERICAN CYANAMID CO
发明人： LEVIN JEREMY IAN , VENKATESAN ARANAPAKAM MUDUMBAI , COLE DEREK CECIL , CHEN JAMES MING , DAVIS JAMIE MARIE , GROSU GEORGE THEODORE
IPC分类号： C07D295/08 , A61K31/16 , A61K31/351 , A61K31/352 , A61K31/381 , A61K31/382 , A61K31/40 , A61K31/4035 , A61K31/4045 , A61K31/4406 , A61K31/445 , A61K31/4453 , A61K31/4465 , A61K31/47 , A61K31/472 , A61P1/04 , A61P9/04 , A61P19/02 , A61P29/00 , A61P31/18 , A61P37/00 , A61P43/00 , C07C259/06 , C07C259/10 , C07C315/04 , C07C317/22 , C07C317/44 , C07C319/20 , C07C323/20 , C07C323/60 , C07D207/34 , C07D209/14 , C07D209/18 , C07D209/48 , C07D211/34 , C07D213/56 , C07D213/82 , C07D215/16 , C07D215/48 , C07D215/54 , C07D217/06 , C07D217/26 , C07D295/092 , C07D309/04 , C07D309/10 , C07D311/84 , C07D333/20 , C07D333/24 , C07D333/58 , C07D333/60 , C07D335/02 , C07D335/04 , C07D333/68 , C07F9/53
摘要： The invention concerns compounds of formula (I) which are useful in treating disease conditions mediated by TNF- alpha , such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease and degenerative cartilage loss.

8. 发明专利

BR0007784A 未知
公开(公告)号：BR0007784A
公开(公告)日：2002-02-05
申请号：BR0007784
申请日：2000-01-27
申请人： AMERICAN CYANAMID CO
发明人： LEVIN JEREMY IAN , VENKATESAN ARANAPAKAM MUDUMBAI , CHEN JAMES MING , ZASK ARIE , SANDANAYAKA VINCENT PREMARANA , DU MILA TI , BAKER JANNIER LEA
IPC分类号： A61K31/351 , A61K31/435 , A61K31/445 , A61K31/496 , A61P19/00 , C07D211/60 , C07D211/62 , C07D211/66 , C07D309/08 , A61K31/35 , C07D401/06 , C07D409/06 , C07D401/12 , C07D413/04 , C07D407/06 , A61P19/02
摘要： Compounds of the formula:useful in the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection.

9. 发明专利

NO20013678A 未知
公开(公告)号：NO20013678A
公开(公告)日：2001-09-20
申请号：NO20013678
申请日：2001-07-26
申请人： AMERICAN CYANAMID CO
发明人： LEVIN JEREMY IAN , CHEN JAMES MING , VENKATESAN ARANAPAKAM MUDUMBAI , ZASK ARIE , SANDANAYAKA VINCENT PREMARANA , DU MILA TI , BAKER JANNIE LEA
IPC分类号： A61K31/351 , A61K31/435 , A61K31/445 , A61K31/496 , A61P19/00 , C07D211/60 , C07D211/62 , C07D211/66 , C07D309/08
CPC分类号： C07D309/08 , A61K31/351 , A61K31/435 , A61K31/445 , A61K31/496 , C07D211/60 , C07D211/62 , C07D211/66

10. 发明专利

NO20013677D0 未知
公开(公告)号：NO20013677D0
公开(公告)日：2001-07-26
申请号：NO20013677
申请日：2001-07-26
申请人： AMERICAN CYANAMID CO
发明人： LEVIN JEREMY IAN , CHEN JAMES MING , VENKATESAN ARANAPAKAM MUDUMBAI , COLE DEREK CECIL , DAVIS JAMIE MARIE , GROSU GEORGE THEODORE
IPC分类号： C07D295/08 , A61K31/16 , A61K31/351 , A61K31/352 , A61K31/381 , A61K31/382 , A61K31/40 , A61K31/4035 , A61K31/4045 , A61K31/4406 , A61K31/445 , A61K31/4453 , A61K31/4465 , A61K31/47 , A61K31/472 , A61P1/04 , A61P9/04 , A61P19/02 , A61P29/00 , A61P31/18 , A61P37/00 , A61P43/00 , C07C259/06 , C07C259/10 , C07C315/04 , C07C317/22 , C07C317/44 , C07C319/20 , C07C323/20 , C07C323/60 , C07D207/34 , C07D209/14 , C07D209/18 , C07D209/48 , C07D211/34 , C07D213/56 , C07D213/82 , C07D215/16 , C07D215/48 , C07D215/54 , C07D217/06 , C07D217/26 , C07D295/092 , C07D309/04 , C07D309/10 , C07D311/84 , C07D333/20 , C07D333/24 , C07D333/58 , C07D333/60 , C07D335/02 , C07D335/04 , C07C
摘要： The invention concerns compounds of formula (I) which are useful in treating disease conditions mediated by TNF- alpha , such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease and degenerative cartilage loss.

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