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

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