title: 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.
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.
authors.forename: Edwin B
authors.initials: EB
authors.lastname: Villhauer
authors.forename: John A
authors.initials: JA
authors.lastname: Brinkman
authors.forename: Goli B
authors.initials: GB
authors.lastname: Naderi
authors.forename: Beth E
authors.initials: BE
authors.lastname: Dunning
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Mangold
authors.forename: Manisha D
authors.initials: MD
authors.lastname: Mone
authors.forename: Mary E
authors.initials: ME
authors.lastname: Russell
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Weldon
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Hughes
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006801:Humans; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D008252:Macaca fascicularis; D008297:Male; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: C121834:1-(((2-((5-cyanopyridin-2-yl)amino)ethyl)amino)acetyl)-2-cyano-(S)-pyrrolidine; D004791:Enzyme Inhibitors; D000960:Hypolipidemic Agents; D009570:Nitriles; D011480:Protease Inhibitors; D011759:Pyrrolidines; D018819:Dipeptidyl Peptidase 4