Discovery of a highly potent series of oxazole-based phosphodiesterase 4 inhibitors.
Substituted quinolyl oxazoles were discovered as a novel and highly potent series of phosphodiesterase 4 (PDE4) inhibitors. Structure-activity relationship studies revealed that the oxazole core, with 4-carboxamide and 5-aminomethyl groups, is a novel PDE4 inhibitory pharmacophore. Selectivity profiles and in vivo biological activity are also reported.
Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. rongze.kuang@spcorp.com
Rongze
R
Kuang
Ho-Jane
HJ
Shue
David J
DJ
Blythin
Neng-Yang
NY
Shih
Danlin
D
Gu
Xiao
X
Chen
John
J
Schwerdt
Ling
L
Lin
Pauline C
PC
Ting
Xiaohong
X
Zhu
Robert
R
Aslanian
John J
JJ
Piwinski
Li
L
Xiao
Daniel
D
Prelusky
Ping
P
Wu
Ji
J
Zhang
Xiang
X
Zhang
Chander S
CS
Celly
Michael
M
Minnicozzi
Motasim
M
Billah
Peng
P
Wang
D000818:Animals; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000187:drug effects; D008958:Models, Molecular; D010080:Oxazoles / Q000737:chemistry / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
D010080:Oxazoles; D010726:Phosphodiesterase Inhibitors; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4