Substituted piperazines as novel dipeptidyl peptidase IV inhibitors.
Incorporation of a fluorophenyl beta-amino amide moiety into piperazine screening lead 2 has resulted in the discovery of a structurally novel series of potent and selective DP-IV inhibitors. Simplification of the molecule and incorporation of multiple fluorine atoms on the phenyl ring has provided low molecular weight analogs such as compound 32, which is a 19nM DP-IV inhibitor with >4000-fold selectivity over QPP.
Brockunier
Linda L
LL
Department of Medicinal Chemistry, Merck & Co. Inc., PO Box 2000, Rahway, NJ 07065, USA. linda_brockunier@merck.com
He
Jiafang
J
Colwell
Lawrence F
LF
Habulihaz
Bahanu
B
He
Huaibing
H
Leiting
Barbara
B
Lyons
Kathryn A
KA
Marsilio
Frank
F
Patel
Reshma A
RA
Teffera
Yohannes
Y
Wu
Joseph K
JK
Thornberry
Nancy A
NA
Weber
Ann E
AE
Parmee
Emma R
ER
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D006207:Half-Life; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D010879:Piperazines; D011480:Protease Inhibitors; D018819:Dipeptidyl Peptidase 4