SAR in the alkoxy lactone series: the discovery of DFP, a potent and orally active COX-2 inhibitor.
Extensive SAR has been established in the alkoxy lactone series and this has lead to the discovery of DFP (5,5-dimethyl-3-(2-propoxy)-4-methanesulfonylphenyl)-2(5H)-furanon e), a potent COX-2 inhibitor exhibiting in vivo efficacy in all models studied.
Leblanc
Y
Y
Merck Frosst Centre for Therapeutic Research, Québec, Canada.
Roy
P
P
Boyce
S
S
Brideau
C
C
Chan
C C
CC
Charleson
S
S
Gordon
R
R
Grimm
E
E
Guay
J
J
Léger
S
S
Li
C S
CS
Riendeau
D
D
Visco
D
D
Wang
Z
Z
Webb
J
J
Xu
L J
LJ
Prasit
P
P
D000284:Administration, Oral; D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism*; D008253:Macaca mulatta; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012453:Saimiri; D013329:Structure-Activity Relationship; D020298:U937 Cells
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases