Aminopiperidine-fused imidazoles as dipeptidyl peptidase-IV inhibitors.
A new series of DPP-4 inhibitors derived from piperidine-fused benzimidazoles and imidazopyridines is described. Optimization of this class of DPP-4 inhibitors led to the discovery of imidazopyridine 34. The potency, selectivity, cross-species DMPK profiles, and in vivo efficacy of 34 is reported.
Edmondson
Scott D
SD
Department of Medicinal Chemistry, Merck & Co. Inc., PO Box 2000, Rahway, NJ 07065, USA. scott_edmondson@merck.com
Mastracchio
Anthony
A
Cox
Jason M
JM
Eiermann
George J
GJ
He
Huaibing
H
Lyons
Kathryn A
KA
Patel
Reshma A
RA
Patel
Sangita B
SB
Petrov
Aleksandr
A
Scapin
Giovanna
G
Wu
Joseph K
JK
Xu
Shiyao
S
Zhu
Bing
B
Thornberry
Nancy A
NA
Roy
Ranabir Sinha
RS
Weber
Ann E
AE
D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray / Q000379:methods; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D015195:Drug Design; D052216:Glucagon-Like Peptide 1 / Q000737:chemistry; D006801:Humans; D006868:Hydrolysis; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008253:Macaca mulatta; D051379:Mice; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D011719:Pyrazines / Q000138:chemical synthesis / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology
D001562:Benzimidazoles; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007093:Imidazoles; D010880:Piperidines; D011719:Pyrazines; D011725:Pyridines; D014230:Triazoles; D052216:Glucagon-Like Peptide 1; C031000:benzimidazole; D000068900:Sitagliptin Phosphate