Synthesis and biological activity of disubstituted 4,5-polymethylenepyrazoles as selective cyclooxygenase-2 inhibitors.
A series of 1,3- and 2,3-disubstituted 4,5-polymethylenepyrazole derivatives were prepared and their inhibitory activities on cyclooxygenase-2 were evaluated. Among the compounds prepared, 1,3-isomer, 3-cyclohexyl-l-(4-fluorophenyl) 4,5-trimethylenepyra-zole (5be) showed the most potent (IC50 = 0.008 microM) inhibitory activity with little selectivity (13-fold) on cyclooxygenase-2.
Yu
J W
JW
College of Pharmacy, Yeungnam University, Kyongsan, Korea.
Kim
H H
HH
Jahng
Y
Y
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007527:Isoenzymes / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse