Title:
【発明の名称】マトリクス金属プロテナイーゼおよびTACEに対する阻害薬としてのβ―スルホンアミドヒドロキサム酸
Document Type and Number:
Japanese Patent JP2001502326
Kind Code:
A
Abstract:
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 (1) where the hydroxamic acid moiety and the sulfonamido moiety are bonded to adjacent carbons on group A where: A is a 5 to 7 membered, monocyclic, non-aromatic heterocyclic ring having from 1 to 2 heteroatoms independently selected from N, O, and S, optionally substituted by R<1>, R<2>, R<3> and R<4>; a -C3-C7-cycloalkyl containing 0-2 double bonds and optionally substituted with R<1>, R<2>, R<3> and R<4>; or -CHR<5>=CHR<6>-; and Z, R<1>, R<2>, R<3>, R<4>, R<5>, R<6>, R<7>, R<8> and R<9> are described in the specification, and the pharmaceutically acceptable salts thereof, and the optical isomers and diastereomers thereof.
Inventors:
Levin, Jeremy Ian
Zask, Ally
Gu, Jansson
Zask, Ally
Gu, Jansson
Application Number:
JP51842498A
Publication Date:
February 20, 2001
Filing Date:
October 08, 1997
Export Citation:
Assignee:
American Cyanamid Company
International Classes:
A61K31/165; A61P9/00; A61P9/10; A61P13/12; A61P15/00; A61P17/00; A61P19/02; A61P25/00; A61P27/02; A61P35/00; C07C257/00; C07C311/20; C07C311/29; A61P1/16; (IPC1-7): C07C311/20; A61K31/165; A61P1/16; A61P9/00; A61P9/10; A61P13/12; A61P15/00; A61P17/00; A61P19/02; A61P25/00; A61P27/02; A61P35/00; C07C311/29
Attorney, Agent or Firm:
Aoyama Ryo (1 person outside)