Synthesis and Antifungal Activity of Butenafine Hydrochloride (KP-363), a New Benzylamine Antifungal Agent

Abstract

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 0.05μg/ml), and also against Aspergillus (15 strains ; MIC range, 0.025 to 0.78μg/ml), Cryptococcus neoformans (4 strains ; MICs 0.78 and 1.56μg/ml) and yeasts of genus Candida (67 strains ; MIC range, 3.13 to >100μg/ml).