Synthesis and antifungal activity of 1,3,2-benzodithiazole S-oxides

J Med Chem. 1994 Mar 4;37(5):572-8. doi: 10.1021/jm00031a005.

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.

MeSH terms

  • Animals
  • Antifungal Agents / chemical synthesis*
  • Antifungal Agents / pharmacokinetics
  • Antifungal Agents / pharmacology
  • Candida / drug effects*
  • Chromatography, High Pressure Liquid
  • Cyclic S-Oxides / chemical synthesis
  • Cyclic S-Oxides / pharmacokinetics
  • Molecular Structure
  • Rats
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis*
  • Thiazoles / pharmacokinetics
  • Thiazoles / pharmacology

Substances

  • Antifungal Agents
  • Cyclic S-Oxides
  • Thiazoles
  • N-benzyl-1,3,2-benzodithiazole S-oxide