A new structural variation on the methanesulfonylphenyl class of selective cyclooxygenase-2 inhibitors.
By inserting an oxygen link between the 3-fluorophenyl and the lactone ring of 5,5-dimethyl-3-(3fluorophenyl)-4-(4-methanesulfonylphenyl)-2 (5H)-furanone 1 (DFU), analogs with enhanced in vitro COX-2 inhibitory potency as well as in vivo potency in models of inflammation were obtained.
Li
C S
CS
Merck Frosst Centre for Therapeutic Research, Pointe-Clarie-Dorval, Quebec, Canada.
Black
W C
WC
Brideau
C
C
Chan
C C
CC
Charleson
S
S
Cromlish
W A
WA
Claveau
D
D
Gauthier
J Y
JY
Gordon
R
R
Greig
G
G
Grimm
E
E
Guay
J
J
Lau
C K
CK
Riendeau
D
D
Thérien
M
M
Visco
D M
DM
Wong
E
E
Xu
L
L
Prasit
P
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D005663:Furans / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D007527:Isoenzymes / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D051381:Rats; D013329:Structure-Activity Relationship
C106876:5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005663:Furans; D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases