α-磺酰基羧酸作为强效基质金属蛋白酶抑制剂的合成与构效关系研究

Synthesis and SAR of alpha-sulfonylcarboxylic acids as potent matrix metalloproteinase inhibitors.

作者信息

Zhang Yue-Mei, Fan Xiaodong, Xiang Bangping, Chakravarty Devraj, Scannevin Robert, Burke Sharon, Karnachi Prabha, Rhodes Kenneth, Jackson Paul

机构信息

Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, 1000 Route 202, Raritan, NJ 08869, USA.

出版信息

Bioorg Med Chem Lett. 2006 Jun 15;16(12):3096-100. doi: 10.1016/j.bmcl.2006.03.065. Epub 2006 May 2.

DOI:10.1016/j.bmcl.2006.03.065

PMID:16632358

Abstract

A series of novel carboxylic acid-based alpha-sulfone MMP inhibitors have been synthesized and the in vitro enzyme SAR is discussed. A potential binding mode in the active site of the MMP-9 homology model was highlighted. These compounds are potent MMP-9 inhibitors and are selective over MMP-1.

摘要

一系列新型基于羧酸的α-砜基质金属蛋白酶（MMP）抑制剂已被合成，并讨论了其体外酶活性的构效关系（SAR）。突出了MMP-9同源模型活性位点中的一种潜在结合模式。这些化合物是有效的MMP-9抑制剂，且对MMP-1具有选择性。