SYNTHESIS AND ANTIFUNGAL ACTIVITY OF BUTENAFINE HYDROCHLORIDE (KP-363), A NEW BENZYLAMINE ANTIFUNGAL AGENT

In screening of new antifungal agents, bis(naphthalenemethyl)amines were found to have more potent antifungal activity than clotrimazole. Studies on their structure-activity relationships indicated that benzylamines had potent antifungal activity. Among them, butenafine hydrochloride (N-p-tert-butylbenzyl-N-methyl-1-naphthalenemethylamine hydrochloride, KP-363) has proved to show the strongest activity. It exhibits a wide spectrum activity in vitro against particularly dermatophytes (87 strains; minimal inhibitory concentration (MIC) range, 0.0015 to 0.05-mu-g/ml), and also against Aspergillus (15 strains; MIC range, 0.025 to 0.78-mu-g/ml), Cryptococcus neoformans (4 strains; MICs 0.78 and 1.56-mu-g/ml) and yeasts of genus Candida (67 strains; MIC range, 3.13 to > 100-mu-g/ml).