Triazolopiperazine-amides as dipeptidyl peptidase IV inhibitors: close analogs of JANUVIA (sitagliptin phosphate).
A series of beta-aminoamides bearing triazolopiperazines has been prepared and evaluated as potent, selective, orally active dipeptidyl peptidase IV (DPP-4) inhibitors. Efforts at optimization of the beta-aminoamide series, which ultimately led to the discovery of JANUVIA (sitagliptin phosphate, compound 1), are described.
Kim
Dooseop
D
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. dooseop_kim@merck.com
Kowalchick
Jennifer E
JE
Edmondson
Scott D
SD
Mastracchio
Anthony
A
Xu
Jinyou
J
Eiermann
George J
GJ
Leiting
Barbara
B
Wu
Joseph K
JK
Pryor
KellyAnn D
KD
Patel
Reshma A
RA
He
Huaibing
H
Lyons
Kathryn A
KA
Thornberry
Nancy A
NA
Weber
Ann E
AE
D000577:Amides / Q000737:chemistry*; D000818:Animals; D054873:Dipeptidyl-Peptidase IV Inhibitors; D010879:Piperazines / Q000737:chemistry*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D011719:Pyrazines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D000068900:Sitagliptin Phosphate; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology
D000577:Amides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D010879:Piperazines; D011480:Protease Inhibitors; D011719:Pyrazines; D014230:Triazoles; D000068900:Sitagliptin Phosphate