Discovery of Alogliptin: A Potent, Selective, Bioavailable, and Efficacious Inhibitor of Dipeptidyl Peptidase IV

Abstract

Alogliptin is a potent, selective inhibitor of the serine\nprotease dipeptidyl peptidase IV (DPP-4). Herein, we describe the\nstructure-based design and optimization of alogliptin and related\nquinazolinone-based DPP-4 inhibitors. Following an oral dose, these\nnoncovalent inhibitors provide sustained reduction of plasma DPP-4\nactivity and a lowering of blood glucose in animal models of diabetes.\nAlogliptin is currently undergoing phase III trials in patients with type\n2 diabetes.