ANTIINFLAMMATORY 2-ARYL-1,3-INDANDIONES

Previously reported antiinflammatory activity for 2-phenyl-1,3-indandione (1) was confirmed in rats. Compound 1 also inhibits blood coagulation in vivo, by inhibiting the hepatic synthesis of prothrombin. However, at the time of measurement of antiedema activity (3 hr post-carrageenin injection) neither 1 nor the other anticoagulants warfarin, bishydroxycoumarin, or 2-pivalyl-1,3-indandione had induced a coagulation defect; of these four compounds only 1 had antiinflammatory activity. The aim of this program was the separation of antiinflammatory from anticoagulant activity in some 2-arylindandiones. All compounds were tested in the rat for inhibition of carrageenin-induced paw edema and for inhibition of prothrombin synthesis. Results showed most nuclear unsubstituted 2-aryl-1,3-indandiones to be inhibitors in both tests; however, fairly large meta substituents on the 2-aryl function diminished anticoagulant activity. In addition, certain substituents in the indane ring successfully removed anticoagulant activity while retaining antiinflammatory activity in many cases. The acidity of those compounds with antiinflammatory activity was found to be restricted to a fairly narrow range. © 1968, American Chemical Society. All rights reserved.