Furo[3,2-b]indole derivatives. V. Synthesis and structure-activity studies of 4-substituted 2-(4-methylpiperazinylcarbonyl)-6-trifluoromethylfuro[3,2- b]indole derivatives with analgesic and antiinflammatory activities.

Abstract

Based on the quantitative structure-activity relationships (QSAR) of 4, 6-disubstituted 2-morpholinocarbonylfuro [3, 2-b] indole derivatives (53 compounds) previously reported, 4-substituted 2- (4-methylpiperazinylcarbonyl) -6-trifluoromethylfuro [3, 2-b] indole derivatives (12 compounds) were synthesized. Their analgesic and antiinflammatory activities were examined by using the acetic acid writhing test in mice and the carrageenin edema test in rats, respectively. Most of these compounds showed potent analgesic and antiinflammatory activities as compared with tiaramide. The QSAR of the furo [3, 2-b] indole derivatives (65 compounds) including the newly synthesized compounds was analyzed by using the adaptive least-squares method. The results confirmed that the QSARs for 2-morpholinocarbonyl derivatives and 2- (4-methylpiperazinylcarbonyl) derivatives can be expressed in one model where the steric nature of the 4-and 6-substituents mainly affects both the analgesic and antiinflammatory potencies.