Jiang Yongwei, Cao Yongbin, Zhang Jun, Zou Yan, Chai Xiaoyun, Hu Honggang, Zhao Qingjie, Wu Qiuye, Zhang Dazhi, Jiang Yuanying, Sun Qingyan
Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Guohe Road 325, Shanghai 200433, People's Republic of China.
Eur J Med Chem. 2011 Jul;46(7):3135-41. doi: 10.1016/j.ejmech.2011.02.001. Epub 2011 Feb 26.
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.
基于细胞色素P450 14α-脱甲基酶（CYP51）活性位点的结构以及唑类抗真菌剂构效关系的结论，合成了一系列氟康唑类似物1-(2-(2,4-二氟苯基)-2-羟基-3-(1H-1,2,4-三唑-1-基)丙基)-1H-1,2,4-三唑-5(4H)-酮。所有化合物均通过红外光谱、高分辨质谱、(1)H核磁共振和(13)C核磁共振光谱分析进行了表征。使用八种人类致病菌种进行的初步体外抗真菌试验结果表明，一些化合物表现出与参考药物氟康唑相当甚至更好的抗真菌活性，并且化合物3i对白色念珠菌表现出显著活性，值得进一步优化。
