2-Pyridinyl-3-(4-methylsulfonyl)phenylpyridines: selective and orally active cyclooxygenase-2 inhibitors.
A series of novel 2-pyridinyl-3-(4-methylsulfonyl)phenylpyridines has been synthesized and evaluated with respect to their ability to inhibit the isozymes of cyclooxygenase, COX-1, and COX-2. Optimum COX-2 activity is observed by introduction of a substituent at C5 of the central pyridine. 5- Chloro-3-(4-methylsulfonyl)phenyl-2-(2-methyl-5-pyridinyl)pyridine 33 was identified as the optimum compound in this series.
Friesen
R W
RW
Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, Québec, Canada.
Brideau
C
C
Chan
C C
CC
Charleson
S
S
Deschênes
D
D
Dubé
D
D
Ethier
D
D
Fortin
R
R
Gauthier
J Y
JY
Girard
Y
Y
Gordon
R
R
Greig
G M
GM
Riendeau
D
D
Savoie
C
C
Wang
Z
Z
Wong
E
E
Visco
D
D
Xu
L J
LJ
Young
R N
RN
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D016466:CHO Cells / Q000187:drug effects / Q000201:enzymology; D006224:Cricetinae; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004487:Edema / Q000188:drug therapy; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011725:Pyridines; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat