Discovery of potent and selective phenylalanine based dipeptidyl peptidase IV inhibitors.
anti-Substituted beta-methylphenylalanine derived amides have been shown to be potent DPP-IV inhibitors exhibiting excellent selectivity over both DPP8 and DPP9. These are among the most potent compounds reported to date lacking an electrophilic trap. The most potent compound among these is 5-oxo-1,2,4-oxadiazole 44, which is a 3 nM DPP-IV inhibitor.
Xu
Jinyou
J
Department of Medicinal Chemistry, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
Wei
Lan
L
Mathvink
Robert
R
He
Jiafang
J
Park
You-Jung
YJ
He
Huaibing
H
Leiting
Barbara
B
Lyons
Kathryn A
KA
Marsilio
Frank
F
Patel
Reshma A
RA
Wu
Joseph K
JK
Thornberry
Nancy A
NA
Weber
Ann E
AE
D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects*; D010649:Phenylalanine / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*
D011480:Protease Inhibitors; D010649:Phenylalanine; D018819:Dipeptidyl Peptidase 4