Substituted tetrahydrofuroyl-1-phenylalanine derivatives as potent and specific VLA-4 antagonists

被引：19
|
作者：
Doherty, GA [1 ]
Yang, GX
Borges, E
Chang, LL
MacCoss, M
Tong, S
Kidambi, U
Egger, LA
McCauley, E
Van Riper, G
Mumford, RA
Schmidt, JA
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 / 11期
关键词：
D O I：
10.1016/S0960-894X(02)00211-1
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of substituted tetra hydrofuroyl-1-phenylalanine derivatives was prepared and evaluated as VLA-4 antagonists. Substitution of the a carbon of the tetrahydrofuran with aryl groups increased the specificity for VLA-4 versus alpha(4)beta(7) while amide substitution increased the potency of the series without increasing the specificity. Substitution of the P carbon of the tetrahydrofuran with keto or amino groups slightly improved the specificity for VLA-4 versus alpha(4)beta(7) but with a significant loss in binding affinity for VLA-4. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：1501 / 1505
页数：5
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