Design and Synthesis of Pyrimidinone and Pyrimidinedione Inhibitors of Dipeptidyl Peptidase IV
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- 作者：Zhiyuan Zhang ; Michael B. Wallace ; Jun Feng ; Jeffrey A. Stafford ; Robert J. Skene ; Lihong Shi ; Bumsup Lee ; Kathleen Aertgeerts ; Andy Jennings ; Rongda Xu ; Daniel B. Kassel ; Stephen W. Kaldor ; Marc Navre ; David R. Webb ; Stephen L. Gwaltney ; II
- 刊名：Journal of Medicinal Chemistry
- 出版年：2011
- 出版时间：January 27, 2011
- 年：2011
- 卷：54
- 期：2
- 页码：510-524
- 全文大小：1244K
- 年卷期：v.54,no.2(January 27, 2011)
- ISSN：1520-4804
文摘
The discovery of two classes of heterocyclic dipeptidyl peptidase IV (DPP-4) inhibitors, pyrimidinones and pyrimidinediones, is described. After a single oral dose, these potent, selective, and noncovalent inhibitors provide sustained reduction of plasma DPP-4 activity and lowering of blood glucose in animal models of diabetes. Compounds 13a, 27b, and 27j were selected for development.