公开(公告)号：US06632946B2

公开(公告)日：2003-10-14

申请号：US09734167

申请日：2000-12-12

申请人： Dennis Bigg ,  Olivier Lavergne ,  Alain Rolland ,  Christophe Lanco ,  Gerard Ulibarri

发明人： Dennis Bigg ,  Olivier Lavergne ,  Alain Rolland ,  Christophe Lanco ,  Gerard Ulibarri

IPC分类号： C07D21378

CPC分类号： C07D213/64 ,  C07D471/14

摘要： The invention relates to new tetracyclic analogues of camptothecin, their preparation processes, their use as medicaments and the pharmaceutical compositions containing them. Said analogues, which include in particular 3-hydroxy-3-(4-oxo-4,6-dihydroindolizino[1,2-b]quinoline-2-yl)pentanoic acid, have a powerful biological activity inhibiting topoisomerase I and/or topoisomerase II.

摘要翻译： 本发明涉及喜树碱的新四环类似物，其制备方法，它们作为药物的用途以及含有他们的药物组合物。 所述类似物，其特别包括3-羟基-3-（4-氧代-4,6-二氢吲哚并[1,2-b]喹啉-2-基）戊酸，具有抑制拓扑异构酶I和/或 拓扑异构酶II。

公开(公告)号：US06197795B1

公开(公告)日：2001-03-06

申请号：US09330717

申请日：1999-06-11

申请人： Jeremy Ian Levin ,  Frances Christy Nelson

发明人： Jeremy Ian Levin ,  Frances Christy Nelson

IPC分类号： C07D21378

CPC分类号： C07D213/79 ,  C07D213/81 ,  C07D233/90 ,  C07D333/38 ,  C07D409/12

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-&agr; converting enzyme (TACE, tumor necrosis factor-&agr; converting enzyme) which are useful for the treatment of diseases in which these enzymes are implicated such as arhritis, 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 the formula where the hydroxamic acid moiety and the sulfonamido moiety are bonded to adjacent carbons on group A where A is defined as: a 5-6 membered heteroaryl having from 1 to 3 heteroatoms independently selected from N, O, and S and optionally substituted by R1, R2 and R3; and Z, R1, R2, R3, R4, R5, R6, R7, R8 and R9 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 治疗这些酶涉及的疾病如肾炎，肿瘤生长和转移，血管生成，组织溃疡，创伤愈合异常，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，圆锥角膜炎 s，干燥综合征，近视眼，眼肿瘤，眼血管生成/新血管形成。 本发明的TACE和MMP抑制邻氨基磺酰氨基芳基异羟肟酸由异羟肟酸部分和亚磺酰氨基部分与基团A上的相邻碳键合的表示，其中A定义为：具有 1至3个独立地选自N，O和S并且任选被R 1，R 2和R 3取代的杂原子;且Z，R 1，R 2，R 3，R 4，R 5，R 6，R 7，R 8和R 9在本说明书中描述， 其药学上可接受的盐及其旋光异构体和非对映体。