根据三唑类抗真菌药物作用靶酶-羊毛甾醇14α-去甲基化酶的三维晶体结构和药物与酶活性位点的对接结果,设计合成了11个1-(1H1,2,4-三唑-1-基)-2-(2,4-二氟苯基)-3-(N-甲基-N取代苄基氨基)-2-丙醇化合物.11个目标化合物均系首次报道.体外抗真菌活性试验结果表明,所有目标化合物对七种致病真菌都有不同程度的抗真菌活性,而且都比氟康唑的体外抗真菌活性好.化合物11的抗菌谱最广,抗真菌活性最高,对新型隐球菌、白色念珠菌、羊毛状小孢子菌和红色毛癣菌的抗菌活性比酮康唑高,有进一步开发的价值.化合物3,4,10也表现出较高的抗真菌活性.%Eleven 1-(1H-1,2,4-triazole)-2-(2,4-diflurophenyl)-3-(N-methyl-N-substituted benzylamino)-2-propanolswere designed and synthesized, on the basis of the crystal structure of P450 cytochrome 14a-sterol demethylase(CYPS1) andthe docking results of inhibitors to the active site of the enzyme. All title compounds were first by reported. Results of prelimi-nary biological tests showed that most of title compounds exhibited activity against the seven common pathogenic fungi. Com-pound 11 showed best antifungal activity with broad antifungal spectrum and proved to be more active against Cryptococcus neo-formans, C andida albicans, Microsporum lanosum and Trichophyton rubrum than ketoconazole. Compounds 3, 10 and 4 alsohad high activities.
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