Pyridazinones as selective cyclooxygenase-2 inhibitors.
Pyridazinone was found to be an excellent core template for selective COX-2 inhibitors. Two potent, selective and orally active COX-2 inhibitors, which were highly efficacious in rat paw edema and rat pyresis models, have been obtained.
Li
Chun Sing
CS
Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe-Claire-Dorval, Quebec, Canada H9R 4P8. chunsing_li@merck.com
Brideau
Christine
C
Chan
Chi Chung
CC
Savoie
Chantal
C
Claveau
David
D
Charleson
Stella
S
Gordon
Robert
R
Greig
Gillian
G
Gauthier
Jacques Yves
JY
Lau
Cheuk K
CK
Riendeau
Denis
D
Thérien
Michel
M
Wong
Elizabeth
E
Prasit
Petpiboon
P
D000818:Animals; D002460:Cell Line; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D004487:Edema / Q000188:drug therapy; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins; D008657:Metabolic Clearance Rate; D011451:Prostaglandin-Endoperoxide Synthases; D011724:Pyridazines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011724:Pyridazines; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat