The discovery of acylated β-amino acids as potent and orally bioavailable VLA-4 antagonists

被引：14
作者：
Lin, LS [1 ]
Kopka, IE
Mumford, RA
Magriotis, PA
Lanza, T
Durette, PL
Kamenecka, T
Young, DN
de Laszlo, SE
McCauley, E
Van Riper, G
Kidambi, U
Egger, LA
Tong, XC
Lyons, K
Vincent, S
Stearns, R
Colletti, A
Teffera, Y
Fenyk-Melody, J
Schmidt, JA
MacCoss, M
Hagmann, WK
机构：
[1] Merek Res Labs, Dept Med Chem, Rahway, NJ 07065 USA
[2] Mereck Res Labs, Dept Inflammat & Rheumatol Res, Rahway, NJ 07065 USA
[3] Merck Res Labs, Dept Drug Metab, Rahway, NJ 07065 USA
[4] Mereck Res Labs, Dept Comparat Med, Rahway, NJ 07065 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 04期
关键词：
D O I：
10.1016/S0960-894X(01)00818-6
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Acylated beta-amino acids are described as potent, specific and orally bioavailable antagonists of VLA-4. The initial lead was identified from a combinatorial library. Subsequent optimization using a traditional medicinal chemistry approach led to significant improvement in potency (up to 8-fold) while maintaining good pharmacokinetic properties. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：611 / 614
页数：4
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