| 摘要: |
| 目的合成1,2,3-三唑侧链取代三唑醇类化合物并考察其体外抗真菌活性。方法设计合成了21个三唑醇类新化合物,所得化合物结构都经过1HNMR、MS确证；选择8种真菌为实验菌株,进行体外抗真菌活性测试。结果所合成的化合物均具有一定的体外抗真菌活性,其中化合物7 ｛1-(1H-1,2,4-三唑-1-基)-2-(2,4二氟苯基)-3-\[N,N-(4-亚甲基-1-取代苄基-1H-1,2,3三唑)\]-2-丙醇｝对白色念珠菌的MIC80值为0.25 μg/ml,是氟康唑活性的4倍,化合物Ⅵ ｛1-(1H-1,2,4-三唑-1-基)-2-(2,4二氟苯基)-3-(N,N-二炔丙基)-2-丙醇｝对白色念珠菌的MIC80值为0.015 6 μg/ml,是氟康唑活性的64倍,是伊曲康唑的4倍。结论利用13偶极加成反应可以方便地在化合物中引入1,2,3-三唑基；较大的侧链结构可能不利于目标化合物活性的提高。 |
| 关键词: 合成 三唑类 抗真菌药 1,3偶极加成反应 |
| DOI：10.3724/SP.J.1008.2010.01114 |
| 投稿时间：2010-05-27修订日期：2010-07-20 |
| 基金项目:国家自然科学基金(20772153), 上海市科委基金(09dZ1976700), 上海市重点学科资助项目(B906). |
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| Design, synthesis, and antifungal activity of 3-substituted triazole derivatives |
| WANG Bao-gang1, ZOU Min-hui1, LI Wen-zhe1, CHAI Xiao-yun2, YU Shi-chong2,,WU Qiu-ye2* |
| (1. Student Team No. 13, Postgraduate School, Second Military Medical University, Shanghai 200433, China;2. Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China) |
| Abstract: |
| ObjectiveTo study the in vitro antifungal activity of triazole alcohols by introduction of 1, 2, 3-triazole as the side chain.MethodsTwenty-one novel triazole alcohol compounds were designed, synthesized, and characterized by 1HNMR and MS spectra.The in vitro antifungal activities of the compounds were evaluated using eight kinds of pathogenic fungi.ResultsAll the synthesized compounds exhibited certain antifungal activities. The MIC80 value of compound 7 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-\[N,N-(1-substituted-benzyl-4-methylene-1H-1,2,3-triazole)\] against Candida albicans was 0.25 μg/ml, with its activity being 4 times that of fluconazole. The MIC80 value of compound Ⅵ 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-(N,N-dipropargyl)-2-propanols against Candida albicans was 0.015 6 μg/ml, with its activity being 64 times that of fluconazole and 4 times that of itraconazole.ConclusionThe 1,2,3-triazole can be efficiently introduced by intermolecular 1,3-dipolar cycloaddition.Large side chains may be a disadvantage for improving the antifungal activity of the title compounds. |
| Key words: synthesis triazoles antifungal agents 1, 3-dipolar cycloaddition |
