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

页码：611 / 614

页数：4

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