2-heterosubstituted-3-(4-methylsulfonyl)phenyl-5-trifluoromethyl pyridines as selective and orally active cyclooxygenase-2 inhibitors.
A series of novel 2-alkoxy, 2-thioalkoxy and 2-amino-3-(4-methylsulfonyl)phenylpyridines has been synthesized and shown to be highly potent and selective cyclooxygenase-2 (COX-2) inhibitors. Structure-activity relationship studies have demonstrated that central pyridine ring substituents play an important role in the COX-2 potency, selectivity vs the COX-1 enzyme, and oral activity.
Merck Frosst Centre For Therapeutic Research, Pointe-Claire-Dorval, Québec, Canada.
D
D
Dubé
C
C
Brideau
D
D
Deschênes
R
R
Fortin
R W
RW
Friesen
R
R
Gordon
Y
Y
Girard
D
D
Riendeau
C
C
Savoie
C C
CC
Chan
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology; D001682:Biological Availability; D016466:CHO Cells; D006224:Cricetinae; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011725:Pyridines; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases