title: Design, synthesis, and biological evaluation of novel 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted benzylamino-2-propanols.
abstract: Based on the results of computational docking to the active site of the cytochrome P450 14alpha-demethylase (CYP51), a series of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted benzylamino-2-propanols as analogs of fluconazole were designed, synthesized, and evaluated as antifungal agents. Results of preliminary antifungal tests against eight human pathogenic fungi in vitro showed that all the title compounds exhibited excellent activities with broad spectrum.
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: Xiaoyun
authors.initials: X
authors.lastname: Chai
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Shichong
authors.initials: S
authors.lastname: Yu
authors.forename: Honggang
authors.initials: H
authors.lastname: Hu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zou
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Zhao
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Dan
authors.forename: Dazhi
authors.initials: D
authors.lastname: Zhang
authors.forename: Qiuye
authors.initials: Q
authors.lastname: Wu
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D020134:Catalytic Domain; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003198:Computer Simulation; D018360:Crystallography, X-Ray / Q000379:methods; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D015195:Drug Design; D015725:Fluconazole / Q000138:chemical synthesis* / Q000494:pharmacology; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D020005:Propanols / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding; D014230:Triazoles / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D005656:Fungal Proteins; D020005:Propanols; D014230:Triazoles; C465525:cytochrome P-450 CYP51, Candida albicans; D015725:Fluconazole; D003577:Cytochrome P-450 Enzyme System