1-(1H-1,2,4-三唑-1-基)-(2,4-二氟苯基)-3-[N-环丙基-N-(4-取代苄基)]-2-丙醇的合成及抗真菌活性

Synthesis and antifungal activity of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-(N-cycloproyl-N-benzyl-amino)-2-propanols

目的:以氟康唑为先导化合物,设计合成新的三唑醇类化合物,并研究其抗真菌活性。方法:引入4位羧酸酯取代的苄基侧链结构,合成一系列目标化合物,所有化合物结构均经MS1、H-NMR等谱确证;选择8种真菌为实验菌株,测定其体外抗真菌活性。结果:合成了15个未见文献报道的目标化合物;所有化合物对所选真菌均表现出了一定的抑菌活性,其中化合物(1),(2)和(3)对除薰烟曲霉菌外的7种菌都表现出了较好的抑菌活性。结论:4位羧酸酯取代的苄基侧链结构的引入对目标化合物的抗菌活性有一定的影响,侧链越短,抑菌活性越好。

Objective： Design and synthesis of novel triazole antifungal derivatives based on the structure of fluconazole. Methods： A 4-earboxylic ester substituted benzyl group introduced and a series title compounds synthesized. All of them were confirmed by MS, L H-NMR, et al. The antifungal activities were also evaluated against the eight tested pathogenic fungi. Results：Fifteen title compounds were synthesized. All title compounds exhibited activity against fungi tested to some extent. Compounds （ 1 ） , （ ：2 ） and （ 3 ） exhibited strong antifungal activities against eight fungi comparable to the control drug itraeonazole except Aspergillus fumigatus. Conclusions ： A benzyl moiety with a group of shorter length substituted on 4-position is required for high activity.