title: Synthesis and antifungal activity of 1,3,2-benzodithiazole S-oxides.
abstract: The preparation of 1,3,2-benzodithiazole S-oxide analogs exhibiting in vitro antifungal activity against several strains of Candida is described. For the preparation of derivatives bearing aromatic substituents, a novel electrophilic aromatic thiolation reaction was utilized which produced substituted aromatic 1,2-dithiol intermediates. The reactions of nucleophiles with the parent heterocyclic system have led to an efficient transamidation process which allows for the direct production of these analogs. The S-oxide bond exhibits poor stereochemical stability and has been found to epimerize under ambient conditions. The structure-activity data report that a side chain of greater than 10 carbons effects a loss in activity as does the placement of polar groups in this chain.
authors.affiliation: Anti-Infective Division, Abbott Laboratories, Abbott Park, Illinois 60064.
authors.forename: L L
authors.initials: LL
authors.lastname: Klein
authors.forename: C M
authors.initials: CM
authors.lastname: Yeung
authors.forename: D E
authors.initials: DE
authors.lastname: Weissing
authors.forename: P A
authors.initials: PA
authors.lastname: Lartey
authors.forename: S K
authors.initials: SK
authors.lastname: Tanaka
authors.forename: J J
authors.initials: JJ
authors.lastname: Plattner
authors.forename: D J
authors.initials: DJ
authors.lastname: Mulford
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D002175:Candida / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003499:Cyclic S-Oxides / Q000138:chemical synthesis / Q000493:pharmacokinetics; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D003499:Cyclic S-Oxides; D013844:Thiazoles; C086207:N-benzyl-1,3,2-benzodithiazole S-oxide