Specific and dual antagonists of α4β1 and α4β7 integrins

被引：23

作者：

Lin, LS

Lanza, T

McCauley, E

Van Riper, G

Kidambi, U

Cao, J

Egger, LA

Mumford, RA

Schmidt, JA

MacCoss, M

Hagmann, WK

机构：

[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck Res Labs, Dept Immunol & Rheumatol Res, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 02期

关键词：

D O I：

10.1016/S0960-894X(01)00705-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

N-(3,5-Dichlorophenylsulfonyl)-(R)-thioprolyl biarylalanine 10a has been identified as a potent and specific antagonist of the alpha(4)beta(1) integrin. Altering the configuration of thioproline from R to S led to a series of dual antagonists of alpha(4)beta(1) and alpha(4)beta(7), and the N-acetyl analogue 8b was found to be the most potent dual antagonist. A binding site model for alpha(4)beta(7) and alpha(4)beta(7) is proposed to explain the structure-activity relationship. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：133 / 136

页数：4

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