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

  • J Med Chem. 2007 May 17;50(10):2297-300. doi: 10.1021/jm070104l.
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 ,  Stephen L Gwaltney 2nd
PMID: 17441705 DOI: 10.1021/jm070104l
Abstract

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.

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