Synthesis of new isoxazoles and dihydroisoxazoles and in vitro evaluation of their antifungal activity.
New 2-(2,4-dihalogenophenyl)-1-(1H-imidazol-1-yl)-3-(isoxazol-5-yl)propan-2-ols and 2-(2,4-dihalogenophenyl)-1-(1H-imidazol-1-yl)-3-(4,5-dihydroisoxazol-5-yl)propan-2-ols were synthesized by 1,3-dipolar cycloaddition between homopropargylic or homoallylic alcohols and in-situ generated nitrile oxide. Their antifungal activity was evaluated against Candida albicans, C. glabrata, Aspergillus fumigatus and an azole-resistant petite mutant of C. glabrata. Preliminary SAR results are discussed.
Laboratoire SONAS, UPRES-EA 921, UFR des Sciences Pharmaceutiques, Angers, France.
Francis
F
Chevreuil
Anne
A
Landreau
Denis
D
Séraphin
Gérald
G
Larcher
Sabine
S
Mallet
Jean-Philippe
JP
Bouchara
Pascal
P
Richomme
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects*; D041221:Candida glabrata / Q000187:drug effects* / Q000235:genetics; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009154:Mutation
D000935:Antifungal Agents; D007555:Isoxazoles