Synthesis and antifungal activity of 1,3,2-benzodithiazole S-oxides.
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.
Klein
L L
LL
Anti-Infective Division, Abbott Laboratories, Abbott Park, Illinois 60064.
Yeung
C M
CM
Weissing
D E
DE
Lartey
P A
PA
Tanaka
S K
SK
Plattner
J J
JJ
Mulford
D J
DJ
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
D000935:Antifungal Agents; D003499:Cyclic S-Oxides; D013844:Thiazoles; C086207:N-benzyl-1,3,2-benzodithiazole S-oxide