Synthesis and structure-activity relationships of phenyl-substituted benzylamine antimycotics: a novel benzylbenzylamine antifungal agent for systemic treatment

Abstract

Derivatives of the benzylamine antimycotics with an extra phenyl ring incorporated in the side chain have been prepared and their antifungal activity evaluated. The potency is strongly dependent on the distance between the two phenyl groups and the type of spacer. Linking the aryl rings with a quaternary carbon atom resulted in the identification of highly active compounds 7f and 12a, having a novel 4-benzylbenzylamine side chain. Compound 7f and its 7-benzo[b]thienyl analogue 12a show significantly enhanced efficacy, in particular against Candida albicans, and are among the most potent allyl/benzylamine antimycotics identified so far. Extended investigations with the benzylbenzylamine derivative 7f revealed that, in addition to the enhanced antimycotic profile, the compound is the first representative of the benzylamine antimycotics suitable for systemic treatment.