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.
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.
Villhauer
Edwin B
EB
Brinkman
John A
JA
Naderi
Goli B
GB
Dunning
Beth E
BE
Mangold
Bonnie L
BL
Mone
Manisha D
MD
Russell
Mary E
ME
Weldon
Stephen C
SC
Hughes
Thomas E
TE
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
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