New 2-sulfonamidothiazoles substituted at C-4: synthesis of polyoxygenatedaryl derivatives and in vitro evaluation of antifungal activity

Polymethoxylated and polyhydroxylated derivatives of 2-amino-4-arylthiazole s bearing a halogenobenzenesulfonamide moiety at position 2 were synthesize d as azole antifungal analogues. X-ray crystallography studies revealed the predominance of the 2-imino-2,3-dihydrothiazole form in the amino/imino ta utomerism. In vitro assays against various pathogenic fungal strains (Candi da and Trichophyton species) showed no activity in comparison to econazole as reference. These results are discussed on the basis of the estimated glo bal lipophilicity of the molecules (Rekker's method) and the p-electron dis tribution (Mulliken population analysis, AM1 method) within the five-member ed heterocycle. (C) 1999 Editions scientifiques et medicales Elsevier SAS.