SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF PHENYL-SUBSTITUTED BENZYLAMINE ANTIMYCOTICS - A NOVEL BENZYLBENZYLAMINE ANTIFUNGAL AGENT FOR SYSTEMIC TREATMENT

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 ary l rings with a quaternary carbon atom resulted in the identification o f highly active compounds 7f and 12a, having a novel 4-benzylbenzylami ne side chain. Compound 7f and its 7-benzo[b]thienyl analogue 12a show significantly enhanced efficacy, in particular against Candida albica ns, and are among the most potent allyl/benzylamine antimycotics ident ified so far. Extended investigations with the benzylbenzylamine deriv ative 7f revealed that, in addition to the enhanced antimycotic profil e, the compound is the first representative of the benzylamine antimyc otics suitable for systemic treatment.