Diprolyl nitriles as potent dipeptidyl peptidase IV inhibitors

被引：36

作者：

Zhao, GH

Taunk, PC

Magnin, DR

Simpkins, LM

Robl, JA

Wang, AY

Robertson, JG

Marcinkeviciene, J

Sitkoff, DF

Parker, RA

Kirby, MS

Hamann, LG

机构：

[1] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Discovery Chem, Princeton, NJ 08543 USA

[2] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Metab Dis, Princeton, NJ 08543 USA

[3] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Chem Enzymol, Princeton, NJ 08543 USA

[4] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Comp Assisted Drug Design, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 18期

关键词：

diprolyl nitriles; dipeptidyl peptidase IV;

D O I：

10.1016/j.bmcl.2005.06.043

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Dipeptidyl peptidase IV (DPP4) is a multifunctional type II transmembrane serine peptidase which regulates various physiological processes, most notably plasma glucose homeostasis by cleaving peptide hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. Inhibition of DPP4 is a potentially valuable therapy for type 2 diabetes. Synthesis and structure activity relationships of a series of substituted diprolyl nitriles are described, leading to the identification of compound 1 with a measured DPP4 K-i of 3.6 nM. (c) 2005 Elsevier Ltd. All rights reserved.

引用

收藏

页码：3992 / 3995

页数：4

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