Discovery of alogliptin: A potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV

被引：352

作者：

Feng, Jun

Zhang, Zhiyuan

Wallace, Michael B.

Stafford, Jeffrey A.

Kaldor, Stephen W.

Kassel, Daniel B.

Navre, Marc

Shi, Lihong

Skene, Robert J.

Asakawa, Tomoko

Takeuchi, Koji

Xu, Rongda

Webb, David R.

Gwaltney, Stephen L., II

机构：

[1] Takeda San Diego Inc, San Diego, CA 92121 USA

[2] Takeda Pharmaceut Co Ltd, Div Pharmaceut Res, Osaka, Japan

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2007年 / 50卷 / 10期

关键词：

D O I：

10.1021/jm070104l

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Alogliptin is a potent, selective inhibitor of the serine protease dipeptidyl peptidase IV (DPP-4). Herein, we describe the structure-based design and optimization of alogliptin and related quinazolinone-based DPP-4 inhibitors. Following an oral dose, these noncovalent inhibitors provide sustained reduction of plasma DPP-4 activity and a lowering of blood glucose in animal models of diabetes. Alogliptin is currently undergoing phase III trials in patients with type 2 diabetes.

引用

页码：2297 / 2300

页数：4

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