Discovery and Structure-Activity Relationships of Piperidinone- and Piperidine-Constrained Phenethylamines as Novel, Potent, and Selective Dipeptidyl Peptidase IV Inhibitors

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• 作者：Zhonghua Pei ; Xiaofeng Li ; Thomas W. von Geldern ; Kenton Longenecker ; Daisy Pireh ; Kent D. Stewart ; Bradley J. Backes ; Chunqiu Lai ; Thomas H. Lubben ; Stephen J. Ballaron ; David W. A. Beno ; Anita J. Ke
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：April 19, 2007
• 年：2007
• 卷：50
• 期：8
• 页码：1983 - 1987
• 全文大小：154K
• 年卷期：v.50,no.8(April 19, 2007)
• ISSN：1520-4804

文摘

Dipeptidyl peptidase IV (DPP4) inhibitors are emerging as a new class of therapeutic agents for the treatmentof type 2 diabetes. They exert their beneficial effects by increasing the levels of active glucagon-like peptide-1and glucose-dependent insulinotropic peptide, which are two important incretins for glucose homeostasis.Starting from a high-throughput screening hit, we were able to identify a series of piperidinone- and piperidine-constrained phenethylamines as novel DPP4 inhibitors. Optimized compounds are potent, selective, andhave good pharmacokinetic profiles.