2,5-diarylisothiazolone: Novel inhibitors of cytokine-induced cartilage destruction

被引：13

作者：

Wright, SW ^{[1
]}

Petraitis, JJ ^{[1
]}

Freimark, B ^{[1
]}

Giannaras, JV ^{[1
]}

Pratta, MA ^{[1
]}

Sherk, SR ^{[1
]}

Williams, JM ^{[1
]}

Magolda, RL ^{[1
]}

Arner, EC ^{[1
]}

机构：

[1] DUPONT MERCK PHARMACEUT CO, WILMINGTON, DE 19880 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 1996年 / 4卷 / 06期

关键词：

D O I：

10.1016/0968-0896(96)00053-3

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of 2,5-diarylisothiazolones is reported that inhibit the IL-lp-induced breakdown of bovine nasal septum cartilage in an organ culture assay. The synthesis and preliminary SAR of these compounds are described. These compounds represent a novel, nonpeptide lead series approach to the mediation of the chronic cartilage breakdown associated with arthritic disease. These compounds are relatively resistant to reductive metabolism by liver microsomal preparations and appear to inhibit cartilage breakdown by interfering with the proteolytic activation of matrix metalloproteinases. Copyright (C) 1996 Elsevier Science Ltd

引用

页码：851 / 858

页数：8