Synthesis and antifungal activity of (E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphtha lenemethanamine (SF 86-327) and related allylamine derivatives with enhanced oral activity.
The allylamine derivatives are a new class of synthetic antifungal agents inhibiting fungal squalene epoxidase. A new subclass, which features an acetylene group conjugated with the allylamine double bond, is characterized by enhanced antifungal activity, especially on oral treatment of guinea pig dermatophytoses. Increased branching of the alkyl group next to the triple bond led to the tert-butylacetylene derivative SF 86-327, a compound with strikingly increased activity in vitro and in vivo, which is now under clinical evaluation. Versatile synthetic routes, comparative biological data, and structure--activity relationships are presented.
D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis*; D003881:Dermatomycoses / Q000188:drug therapy; D005658:Fungi / Q000187:drug effects; D006168:Guinea Pigs; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D009281:Naphthalenes / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D000077291:Terbinafine; D014005:Tinea / Q000188:drug therapy; D014249:Trichophyton / Q000187:drug effects
D000935:Antifungal Agents; D009281:Naphthalenes; D000077291:Terbinafine