Discovery of Alogliptin: A Potent, Selective, Bioavailable, and Efficacious Inhibitor of Dipeptidyl Peptidase IV
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- 作者：Jun Feng ; Zhiyuan Zhang ; Michael B. Wallace ; Jeffrey A. Stafford ; Stephen W. Kaldor ; Daniel B. Kassel ; Marc Navre ; Lihong Shi ; Robert J. Skene ; Tomoko Asakawa ; Koji Takeuchi ; Rongda Xu ; David R. Webb
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：May 17, 2007
- 年：2007
- 卷：50
- 期：10
- 页码：2297 - 2300
- 全文大小：559K
- 年卷期：v.50,no.10(May 17, 2007)
- ISSN：1520-4804
文摘
Alogliptin is a potent, selective inhibitor of the serineprotease dipeptidyl peptidase IV (DPP-4). Herein, we describe thestructure-based design and optimization of alogliptin and relatedquinazolinone-based DPP-4 inhibitors. Following an oral dose, thesenoncovalent inhibitors provide sustained reduction of plasma DPP-4activity and a lowering of blood glucose in animal models of diabetes.Alogliptin is currently undergoing phase III trials in patients with type2 diabetes.