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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收藏
页码：43 / 46
页数：4
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