4-Amino cyclohexylglycine analogues as potent dipeptidyl peptidase IV inhibitors

被引：43

作者：

Parmee, ER

He, JF

Mastracchio, A

Edmondson, SD

Colwell, L

Eiermann, G

Feeney, WP

Habulihaz, B

He, HB

Kilburn, R

Leiting, B

Lyons, K

Marsilio, F

Patel, RA

Petrov, A

Di Salvo, J

Wu, JK

Thornberry, NA

Weber, AE

机构：

[1] Merck & Co Inc, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck & Co Inc, Dept Metab Dis, Rahway, NJ 07065 USA

[3] Merck & Co Inc, Dept Anim Pharmacol, Rahway, NJ 07065 USA

[4] Merck & Co Inc, Dept Immunol & Rheumatol, Rahway, NJ 07065 USA

[5] Merck & Co Inc, Dept Comparat Med, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 01期

关键词：

D O I：

10.1016/j.bmcl.2003.10.016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Substituted 4-amino cyclohexylglycine analogues were evaluated for DP-IV inhibitory properties. Bis-sulfonamide 15e was an extremely potent 2.6 nM inhibitor of the enzyme with excellent selectivity over all counterscreens. 2,4-Difluorobenzenesulfonamide 15b and 1-naphthyl amide 16b, however, combined an acceptable in vitro profile with good pharmacokinetic properties in the rat, and 15b was orally efficacious at 3 mpk in an OGTT in lean mice. (C) 2003 Elsevier Ltd. All rights reserved.

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页码：43 / 46

页数：4

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