Allylamine Antifungal Drugs

The allylammes constitute a recently developed class of synthetic antimycotics characterized functionally by their action as squalene epoxidase inhibitors.1 Figure 6–1 shows the structures of three representative allylamines. Naftifine, the first of these compounds to be discovered, was first synthesized in 1974,2 and its antifungal properties were identified during routine screening. The potent antifungal activity of naftifine in vitro3 and in vivo4 led to its clinical development, and this drug has been marketed since 1985 as a topical antimycotic. Naftifine provided the basis for an extensive program of chemical derivatization5–8 aimed at improving the antimycotic efficacy, especially with regard to oral administration. This goal was achieved in the form of terbinafine (SF 86–327), 1,6–13 the efficacy of which has now been confirmed in numerous clinical studies involving both topical and oral application. Parallel to this development, detailed investigations were carried out concerning the mechanism of action of the allylamines,14–26 including much basic research on the biochemistry of ergosterol biosynthesis in pathogenic fungi.