The discovery of small molecule carbamates as potent dual α4β1/α4β7 integrin antagonists

被引：18

作者：

Chang, LL ^{[1
]}

Truong, Q

Mumford, RA

Egger, LA

Kidambi, U

Lyons, K

McCauley, E

Van Riper, G

Vincent, S

Schmidt, JA

MacCoss, M

Hagmann, WK

机构：

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

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

[3] Merck Res Labs, Dept Drug Metab, 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)00710-7

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The alpha(4)beta(1) and alpha(4)beta(7) integrins are implicated in several inflammatory disease states. Systematic SAR studies of an alpha(4)beta(1)-specific arylsulfonyl-Pro-Tyr lead led to the identification of a new alpha(4)beta(7) binding site, best captured by O-carbamates of Tyr for this structural class. Several compounds showed a 200- to 400-fold improvement in alpha(4)beta(7) binding affinity while maintaining subnanomolar alpha(4)beta(1) activity, for example 21, VCAM-Ig alpha(4)beta(1) IC50 = 0.13 nM. VCAM-Ig alpha(4)beta(7) IC50 = 1.92 nM. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：159 / 163

页数：5

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