Terphenyl cyclooxygenase-2 (COX-2) inhibitors: optimization of the central ring and o-biphenyl analogs.
The discovery of terphenyl derivatives as highly selective COX-2 inhibitors resulted from our efforts to overcome poor pharmacokinetics demonstrated by the COX-2 selective diarylthiophene DuP 697 [2-bromo-4-(4'-sulfonylmethyl)phenyl-5-(4'-fluoro)phenylthiophe ne]. Detailed SAR related to the ortho-biphenyls and variants of the central ring are described herein.
Pinto
D J
DJ
The DuPont Pharmaceutical Company, Wilmington, DE 19880-0500, USA.
Batt
D G
DG
Pitts
W J
WJ
Petraitis
J J
JJ
Orwat
M J
MJ
Wang
S
S
Jetter
J W
JW
Sherk
S R
SR
Houghton
G C
GC
Copeland
R A
RA
Covington
M B
MB
Trzaskos
J M
JM
Magolda
R L
RL
D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics; D007527:Isoenzymes / Q000187:drug effects; D015394:Molecular Structure; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000493:pharmacokinetics
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013876:Thiophenes; C064874:DuP 697; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases