1-[2-[(5-cyanopyridin-2-yl)amino]-ethylamino]acetyl-2-(S)-pyrrolidine-carbonitrile:: A potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties

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-I-V 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-I-V inhibitor that has excellent oral bioavailability and potent antihyperglycemic activity.