1-[2-[(5-Cyanopyridin-2-yl)amino]ethylamino]acetyl-2-(S)-pyrrolidinecarbonitrile: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties

  • J Med Chem. 2002 Jun 6;45(12):2362-5. doi: 10.1021/jm025522z.
Edwin B Villhauer ,  John A Brinkman ,  Goli B Naderi ,  Beth E Dunning ,  Bonnie L Mangold ,  Manisha D Mone ,  Mary E Russell ,  Stephen C Weldon ,  Thomas E Hughes
PMID: 12036346 DOI: 10.1021/jm025522z
Abstract

Dipeptidyl Peptidase IV (DPP-IV) inhibition has the potential to become a valuable therapy for type 2 diabetes. We report the first use of solid-phase synthesis in the discovery of a new DPP-IV inhibitor class and a solution-phase synthesis that is practical up to the multikilogram scale. One compound, NVP-DPP728 (2), is profiled as a potent, selective, and short-acting DPP-IV inhibitor that has excellent oral bioavailability and potent antihyperglycemic activity.