Design, synthesis, and biological evaluation of triazolopiperazine-based beta-amino amides as potent, orally active dipeptidyl peptidase IV (DPP-4) inhibitors.
Various beta-amino amides containing triazolopiperazine heterocycles have been prepared and evaluated as potent, selective, orally active dipeptidyl peptidase IV (DPP-4) inhibitors. These compounds display excellent oral bioavailability and good overall pharmacokinetic profiles in preclinical species. Moreover, in vivo efficacy in an oral glucose tolerance test in lean mice is demonstrated.
Kowalchick
Jennifer E
JE
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. jennifer_kowalchick@yahoo.com
Leiting
Barbara
B
Pryor
KellyAnn D
KD
Marsilio
Frank
F
Wu
Joseph K
JK
He
Huaibing
H
Lyons
Kathryn A
KA
Eiermann
George J
GJ
Petrov
Aleksandr
A
Scapin
Giovanna
G
Patel
Reshma A
RA
Thornberry
Nancy A
NA
Weber
Ann E
AE
Kim
Dooseop
D
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D018360:Crystallography, X-Ray; D054873:Dipeptidyl-Peptidase IV Inhibitors; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D008958:Models, Molecular; D010879:Piperazines / Q000737:chemistry*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats