title: Synthesis and Structure-Activity Relationships of Novel Benzylamine-Type Antifungals as Butenafine-Related Antimycotics.
abstract: Benzylamine-type antimycotics like naftifine, butenafine, or terbinafine are a well-known class of antimycotics since the 1980s. The following paper describes the synthesis and biological evaluation of a series of novel benzylamine-type antimycotics characterized by an isooctyl side chain and various substituents at the benzylamine moiety. The compounds were prepared from benzaldehyde derivatives and 2-amino-6-methylheptane by reductive amination with sodium triacetoxyborohydride and subsequent precipitation with hydrogen chloride. The antimycotic activity of the resulting compounds was evaluated in an agar diffusion assay against the yeasts C. glabrata and Yarrowia lipolytica, the mold Aspergillus niger and the dermatophyte H. burtonii. The compounds were also tested in a microdilution assay against the yeast Candida glabrata and the dermatophyte H. burtonii to determine the minimal inhibitory concentrations (MIC). Compounds with an aromatic ether side chain or a short alkyl ether side chain showed significant antimycotic activity against C. glabrata, comparable to terbinafine or clotrimazole.
authors.affiliation: Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Jürgen
authors.identifier: http://orcid.org/0000-0002-2464-2011
authors.initials: J
authors.lastname: Krauss
authors.forename: Martina
authors.initials: M
authors.lastname: Stadler
authors.forename: Franz
authors.initials: F
authors.lastname: Bracher
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001234:Aspergillus niger / Q000187:drug effects; D001596:Benzylamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D041221:Candida glabrata / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology; D004718:Saccharomycetales / Q000187:drug effects; D013329:Structure-Activity Relationship; D025062:Yarrowia / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D001596:Benzylamines; D009281:Naphthalenes; C067594:butenafine; C030796:benzylamine
keywords: Antimicrobial activity; Antimycotics; Benzylamines; Reductive amination