2,3-Dihydrobenzofuran-2-ones: a new class of highly potent antiinflammatory agents.
A series of 2,3-dihydrobenzofuran-2-one analogues of the mold metabolite wortmannin, which is a powerful antiinflammatory compound, was synthesized. Most of these compounds were tested for their ability to inhibit the carrageenin paw edema and the adjuvant-induced arthritis of the rat and for their ability to inhibit prostaglandin synthesis in vitro. Indomethacin and diclofenac were used as references. The results show that compounds bearing an alkyl or aryl group in position 6 and an additional substituent, preferably chlorine, in position 5 are very powerful antiinflammatory agents and inhibitors of prostaglandin synthesis. The most active among these compounds, 5-chloro-6-cyclohexyl-2,3-dihydrobenzofuran-2-one, was significantly more potent than diclofenac in all testing models, more powerful than indomethacin in inhibiting acute inflammation and prostaglandin synthesis, and somewhat less potent than the latter compound in the adjuvant arthritis model.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis*; D001169:Arthritis, Experimental / Q000188:drug therapy; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D003864:Depression, Chemical; D004487:Edema / Q000188:drug therapy; D066298:In Vitro Techniques; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D001572:Benzofurans; D011453:Prostaglandins; C012529:5-chloro-6-cyclohexyl-2,3-dihydrobenzofuran-2-one