Synthesis and biological evaluation of 3-heteroaryloxy-4-phenyl-2(5H)-furanones as selective COX-2 inhibitors.
A series of 3-heteroaryloxy4-phenyl-2-5H)-furanones were prepared and evaluated for their potency and selectivity as COX-2 inhibitors. This led to the identification of L-778,736 as a potent, orally active and selective inhibitor of the COX-2 enzyme.
Lau
C K
CK
Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, Québec, Canada.
Brideau
C
C
Chan
C C
CC
Charleson
S
S
Cromlish
W A
WA
Ethier
D
D
Gauthier
J Y
JY
Gordon
R
R
Guay
J
J
Kargman
S
S
Li
C S
CS
Prasit
P
P
Riendeau
D
D
Thérien
M
M
Visco
D M
DM
Xu
L
L
D000818:Animals; D001682:Biological Availability; D016466:CHO Cells; D006224:Cricetinae; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D005663:Furans / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D011725:Pyridines / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005663:Furans; D007527:Isoenzymes; C401741:L 778736; D008565:Membrane Proteins; D011725:Pyridines; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases