SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF NAPHTHALENE-SUBSTITUTED DERIVATIVES OF THE ALLYLAMINE ANTIMYCOTIC TERBINAFINE

Derivatives of the allylamine antimycotic terbinafine (1) with varied substitution at the naphthalene ring system have been prepared, and th eir antifungal activity has been evaluated. In general, the potency is strongly dependent on the bulkiness of the substituent. Only hydrogen or in some cases fluorine are tolerated as substituents at positions 2-4 and 6-8 of the naphthalene moiety, whereas 5-substituents may be l arger in size (F, Cl, Br, Me). Derivatives with fluorine at positions 3, 5, and 7 or chlorine at position 5 showed enhanced activity against yeasts relative to 1. This increase in sensitivity could be intensifi ed by simultaneous introduction of two fluoro substituents at position s 5 and 7. Compound 7q demonstrated 8-to 16-fold improved potency agai nst Aspergillus fumigatus, Candida albicans, and Candida parapsilosis.