Studies on anti-inflammatory agents. V. Synthesis and pharmacological properties of 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4- (methylsulfinyl)phenyl]pyrazole and related compounds

Article abstract of DOI:10.1248/cpb.45.1475

A series of novel 1,5-diphenylpyrazole derivatives hearing hydrophilic substituents was prepared. The anti-inflammatory and analgesic activities of these compounds were evaluated by using the adjuvant arthritis and Randall- Selitto assays in rats, and the structure-activity relationships were studied. The optimal compound was 3-(difluoromethyl)-1 -(4-methoxyphenyl)-5- [4-(methylsulfinyl)phenyl]pyrazole (10) with oral Ed₅₀ values of 0.31 and 2.6mg/kg on adjuvant-induced arthritis and carrageenin-induced foot edema, respectively. Compound 10 showed analgesic activities not only toward inflamed paw but also toward normal paw (ED₃₀=0.55 and 1.8mg/kg, respectively) in the Randall-Selitto assay, and moreover, 10 was effective in the tail-pinch assay (ED₅₀=21 mg/kg) similarly to morphine. The asymmetric synthesis and pharmacological properties of the enantiomers of 10 are also reported.

Full text of DOI:10.1248/cpb.45.1475

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