Synthesis and structure-activity relationships of naftifine-related allylamine antimycotics

• Published in: Journal of medicinal chemistry Vol. 29; no. 1; pp. 112 - 125
• Main Authors: Stuetz, Anton, Georgopoulos, Apostolos, Granitzer, Waltraud, Petranyi, Gabor, Berney, Daniel
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01-01-1986
• Subjects: Allylamine - analogs & derivatives; Allylamine - chemical synthesis; Allylamine - pharmacology; Allylamine - therapeutic use; Amines - chemical synthesis; Amines - pharmacology; Amines - therapeutic use; Animals; Antifungal Agents - chemical synthesis; Antifungal Agents - pharmacology; Antifungal Agents - therapeutic use; Aspergillus fumigatus - drug effects; Biological and medical sciences; Candida - drug effects; Chemical Phenomena; Chemistry; Epidermophyton - drug effects; General pharmacology; Guinea Pigs; Medical sciences; Microsporum - drug effects; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Sporothrix - drug effects; Structure-Activity Relationship; Tinea - drug therapy; Trichophyton - drug effects; Antifungal agent; Structure activity relation; Aliphatic compound; Tertiary amine; Bicyclic compound; Benzenic compound; Condensed benzenic compound; Allylic compound
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00151a019

Naftifine (1) is the first representative of the new antifungal allylamine derivatives. Its biological activity is strictly bound to specific structural requirements that are unrelated to those of known antifungals. A tertiary allylamine function seems to be a prerequisite for activity against fungi. By systematic variation of the individual structural elements in 1, detailed structure-activity relationships are defined in which the phenyl ring is the structural feature permitting the widest variations. Versatile synthetic routes to allylamine derivatives and comparative biological data are presented.