Synthesis and antiinflammatory activities of 3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-ones.
A series of 3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-ones was synthesized and evaluated as candidate antiinflammatory/analgesic agents as well as dual inhibitors of prostaglandin and leukotriene synthesis. Some compounds that showed dual inhibitory activity were found to possess equipotent antiinflammatory activities to indomethacin, with reduced ulcerogenic effects. One of the compounds, N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-o ne, was found to have a wider safety margin than indomethacin or piroxicam, and was selected for detailed evaluation as a candidate drug for clinical application.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D001597:Benzylidene Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D006801:Humans; D008297:Male; D011458:Prostaglandins E / Q000096:biosynthesis; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001597:Benzylidene Compounds; D016861:Cyclooxygenase Inhibitors; D011458:Prostaglandins E; D011760:Pyrrolidinones; D015232:Dinoprostone