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Download fileSynthesis of 4,5-Diaryl-1H-pyrazole-3-ol Derivatives as Potential COX-2 Inhibitors
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posted on 2004-10-15, 00:00 authored by Meena V. Patel, Randy Bell, Sandra Majest, Rodger Henry, Teodozyj Kolasa4,5-Diaryl-1H-pyrazole-3-ol was utilized as a versatile template to synthesize several classes of
compounds such as pyrazolo-oxazines 7, pyrazolo-benzooxazines 9, pyrazolo-oxazoles 10, and its
analogues 11a−c as potential COX-2 inhibitors. Compounds 11b,c were successfully synthesized
with use of pyridinium p-toluenesulfonate mediated cyclization of the ketal intermediate. Diaryl-pyrazolo-benzooxazepine analogues were synthesized by using Cu-mediated cyclization of the
O-alkylated arylbromide intermediate. Arylsulfonamides were synthesized efficiently on a large
scale with 4-[4-(4-fluorophenyl)-5-hydroxy-2H-pyrazol-3-yl]benzenesulfonamide 31 template readily
synthesized from commercially available 4-sulfamoyl benzoic acid 29. The structure of a representative compound from each class was confirmed by X-ray crystallography. Selected compounds tested
for inhibitory activity against COX-1 and COX-2 enzymes showed good selectivity for COX-2 versus
COX-1 enzyme.