Synthesis and activity of a new methoxytetrahydropyran derivative as dual cyclooxygenase-2/5-lipoxygenase inhibitor.
Dual COX-2/5-LO inhibitors are described as potential new therapeutic agents for inflammatory diseases. A surprisingly potent effect of a 5-LO pharmacophoric group on the COX-2 inhibition is presented as well as pharmacological in vitro and in vivo results.
Barbey
Sabine
S
Laboratoires Innothera, avenue P. Vaillant-Couturier, BP 10, 94110, Arcueil, France.
Goossens
Laurence
L
Taverne
Thierry
T
Cornet
Joséphine
J
Choesmel
Valérie
V
Rouaud
Céline
C
Gimeno
Gilles
G
Yannic-Arnoult
Sylvie
S
Michaux
Catherine
C
Charlier
Caroline
C
Houssin
Raymond
R
Hénichart
Jean Pierre
JP
D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D006098:Granulocytes / Q000187:drug effects; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D008297:Male; D009000:Monocytes / Q000187:drug effects; D012516:Osteosarcoma / Q000188:drug therapy; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000494:pharmacology*
C461195:3-(3-fluoro-5-(4-(4-methoxytetrahydropyranyl))phenoxymethyl)-1-(4-methylsulfonylphenyl)-5-phenyl-1H-pyrazole; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D013450:Sulfones; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone