title: Design, synthesis and antifungal evaluation of 1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-1H-1,2,4-triazol-5(4H)-one.
abstract: Based on the structure of the active site of cytochrome P450 14α-demethylase (CYP51) and the conclusions of the structure-activity relationships of azole antifungals, a series of 1-(2-(2,4-difluoro-phenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-1H-1,2,4-triazol-5(4H)-one of fluconazole analogs was synthesized. All compounds were characterized by IR, HRMS, (1)HNMR and (13)C NMR spectroscopic analysis. Results of preliminary antifungal in vitro test using eight human pathogenic species showed that some compounds displayed comparable or even better antifungal activities than reference drug fluconazole and that compound 3i exhibited significant activity against Candida albicans being worthy of further optimization.
authors.affiliation: Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Guohe Road 325, Shanghai 200433, People's Republic of China.
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Cao
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zou
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Chai
authors.forename: Honggang
authors.initials: H
authors.lastname: Hu
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Zhao
authors.forename: Qiuye
authors.initials: Q
authors.lastname: Wu
authors.forename: Dazhi
authors.initials: D
authors.lastname: Zhang
authors.forename: Yuanying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Sun
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D015725:Fluconazole / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D058886:Sterol 14-Demethylase / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D005656:Fungal Proteins; D014230:Triazoles; D015725:Fluconazole; D058886:Sterol 14-Demethylase