Discovery of 3-aminopiperidines as potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitors

被引：27
|
作者：
Cox, Jason M.
Harper, Bart
Mastracchio, Anthony
Leiting, Barbara
Roy, Ranabir Sinha
Patel, Reshma A.
Wu, Joseph K.
Lyons, Kathryn A.
He, Huaibing
Xu, Shiyao
Zhu, Bing
Thornberry, Nancy A.
Weber, Ann E.
Edmondson, Scott D.
机构：
[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA
[2] Merck Res Labs, Dept Metab Disorders, Rahway, NJ 07065 USA
[3] Merck & Co Inc, Dept Drug Metab, Rahway, NJ 07065 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 16期
关键词：
dipeptidyl peptidase IV; DPP-4; DPP8; DPP9; QPP; aminopiperidine;
D O I：
10.1016/j.bmcl.2007.05.087
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Substituted 3-aminopiperidines 3 were evaluated as DPP-4 inhibitors. The inhibitors showed good DPP-4 potency with Superb selectivity over other peptidases (QPP, DPP8, and DPP9). Selected DPP-4 inhibitors were further evaluated for their hERG potassium channel, calcium channel, Cyp2D6, and pharmacokinetic profiles. (c) 2007 Elsevier Ltd. All rights reserved.
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页码：4579 / 4583
页数：5
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