Discovery of potent, selective, and orally bioavailable oxadiazole-based dipeptidyl peptidase IV inhibitors.
A novel series of oxadiazole based amides have been shown to be potent DPP-4 inhibitors. The optimized compound 43 exhibited excellent selectivity over a variety of DPP-4 homologs.
Xu
Jinyou
J
Department of Medicinal Chemistry, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. Jinyou_Xu@merck.com
Wei
Lan
L
Mathvink
Robert J
RJ
Edmondson
Scott D
SD
Eiermann
George J
GJ
He
Huaibing
H
Leone
Joseph F
JF
Leiting
Barbara
B
Lyons
Kathryn A
KA
Marsilio
Frank
F
Patel
Reshma A
RA
Patel
Sangita B
SB
Petrov
Aleksandr
A
Scapin
Giovanna
G
Wu
Joseph K
JK
Thornberry
Nancy A
NA
Weber
Ann E
AE
D000284:Administration, Oral; D000818:Animals; D001665:Binding Sites; D001682:Biological Availability; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D010069:Oxadiazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D054873:Dipeptidyl-Peptidase IV Inhibitors; D051638:Ether-A-Go-Go Potassium Channels; D010069:Oxadiazoles; D011480:Protease Inhibitors