1-[2-(2,4-difluorophenyl)-2,3-epoxypropyl]-1H-1,2,4-triazole methanesulfonate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[2-(2,4-difluorophenyl)-2,3-epoxypropyl]-1H-1,2,4-triazole methanesulfonate
• 英文别名: 2-[[2-(2,4-difluorophenyl)oxiran-2-yl]methyl]-1H-1,2,4-triazol-2-ium;methanesulfonate
• 化学式: CH₄O₃S*C₁₁H₉F₂N₃O
• 分子量: 333.316
• InChiKey: NJBRNNOGZPVNNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.99
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-[2-(2,4-difluorophenyl)-2,3-epoxypropyl]-1H-1,2,4-triazole methanesulfonate 在 4-二甲氨基吡啶 、 一水合肼 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 8.5h， 生成 N-(4-(4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl]piperazin-1-yl)-3-fluoro-phenyl)-2-phenylacetamide
  参考文献：
  名称：

  Design, synthesis and antifungal activities of novel 1,2,4-triazole derivatives

  摘要：

  A series of novel 1,2,4-triazole derivatives with a 4-(4-substitutedphenyl) piperazine side chain were designed and synthesized based on the structure of lanosterol 14 alpha-demethylase (CYP51). Their antifungal activities against eight human pathogenic fungi were evaluated in vitro by measuring the minimal inhibitory concentrations. Nearly all tested compounds were found to be more potent against Candida albicans than control drug fluconazole. Noticeably, the MIC80 value of compounds 6,7,9,14 and 29 is 16 times lower than that of voriconazole against C. albicans. The activities of compounds 7 and 21 against Cryptococcus neoformans in vitro are comparable to that of voriconazole with a MIC80 value of 0.0156 mu g/mL. Moreover, the molecular model for the binding between compound 7 and the active site of CACYP51 was provided based on the computational docking results. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.02.042
• 作为产物：
  描述：

  1,3-二氟苯 在 aluminum (III) chloride 、 trimethylsulfoxonium iodide 、 碳酸氢钠 、 cetylmonomethylammonium bromide 、 sodium hydroxide 作用下， 以 甲苯 为溶剂， 反应 14.0h， 生成 1-[2-(2,4-difluorophenyl)-2,3-epoxypropyl]-1H-1,2,4-triazole methanesulfonate
  参考文献：
  名称：

  新型三唑衍生物的合成及抗真菌活性

  摘要：

  一系列新型唑类 (a-v) 是氟康唑的类似物，通过点击反应被设计和合成为潜在的抗真菌剂。合成新型 1,2,3-三唑基连接的三唑抗真菌衍生物 a-v 的点击反应方法是通过 Cu(I) 催化的炔丙基化中间体 5 与取代的叠氮甲基苯的 1,3-偶极环加成反应实现的。此外，测试的目标化合物可以增加抗真菌活性。

  DOI：

  10.1007/s12272-011-1009-z

文献信息

• Synthesis and Evaluation of Some Substituted Heterocyclic Fluconazole Analogues as Antifungal Agents
  作者：Shudong Wang、Lei Zhang、Yongsheng Jin、Jin Hao Tang、Hua Su、Shichong Yu、Haixiang Ren

  DOI：10.14233/ajchem.2014.15956

  日期：——

  A new series of fluconazole analogues of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluoro-phenyl)-3-4-(substituted-heterocyclic ring-1H-1,2,3-triazol-1-yl)-2-propanols (1-10) were designed, synthesized and evaluated as antifungal agents. Preliminary antifungal tests showed that most of the title compounds exhibited moderate activity with broad spectrum against eight human pathogenic fungi in vitro, compounds 1 and 6 had the best antifungal activity against Candida albicans with the value of MIC80 = 0.5 μg/mL respectively.

  设计、合成了1-(1H-1,2,4-三唑-1-基)-2-(2,4-二氟苯基)-3-4-(取代杂环-1H-1,2,3-三唑-1-基)-2-丙醇(1-10)系列氟康唑类似物，并评价了其抗真菌活性。初步抗真菌测试显示，大多数标题化合物对8种人体致病真菌具有中等活性且谱广，其中化合物1和6对白色念珠菌显示出最佳的抗真菌活性，MIC80值分别达到0.5 μg/mL。
• Synthesis and antifungal activity of the novel triazole derivatives containing 1,2,3-triazole fragment
  作者：Shichong Yu、Nan Wang、Xiaoyun Chai、Baogang Wang、Hong Cui、Qingjie Zhao、Yan Zou、Qingyan Sun、Qingguo Meng、Qiuye Wu

  DOI：10.1007/s12272-013-0063-0

  日期：2013.10

  A series of fluconazole analogues containing 1,2,3-triazole fragment have been designed and synthesized on the basis of the active site of the cytochrome P450 14α-demethylase (CYP51). Their structures were characterized by 1H NMR, 13C NMR and LC–MS. The MIC80 values indicate that the target compounds 1a–r showed higher activities against nearly all the fungi tested to some extent except against Aspergillus fumigatus. Compounds 1c, e, f, l and p showed 128 times higher activity (with the MIC80 value of 0.0039 mg/mL) than that of fluconazole against Candida albicans and also showed higher activity than that of the other positive controls.

  基于细胞色素P450 14α-去甲基化酶（CYP51）的活性位点，设计并合成了一系列含有1,2,3-三唑片段的氟康唑类似物。通过1H NMR、13C NMR和LC-MS对其结构进行了表征。MIC80值表明，目标化合物1a-r对几乎所有测试的真菌都显示出更高的活性，仅对烟曲霉（Aspergillus fumigatus）活性有限。化合物1c、e、f、l和p对白色念珠菌（Candida albicans）的活性比氟康唑高出128倍（MIC80值为0.0039 mg/mL），并且其活性也优于其他阳性对照药物。
• New azoles with antifungal activity: Design, synthesis, and molecular docking
  作者：Xiaoyun Chai、Jun Zhang、Yongbing Cao、Yan Zou、Qiuye Wu、Dazhi Zhang、Yuanying Jiang、Qingyan Sun

  DOI：10.1016/j.bmcl.2010.12.006

  日期：2011.1

  excellent activities, a series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluoro-phenyl)-3-[(4-substituted phenyl)-piperazin-1-yl]-propan-2-ols 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. Moreover, a molecular model for

  为了寻找许多具有优异活性的目标化合物，一系列1-（1 H -1,2,4-三唑-1-基）-2-（2,4-二氟-苯基）-3-[（设计，合成并评价了4-取代的苯基）-哌嗪-1-基]-丙烷-2-醇作为抗真菌剂。初步针对八种人类病原性真菌的抗真菌试验结果表明，所有标题化合物均具有出色的广谱活性。此外，基于计算对接结果，提供了5a与CACYP51活性位点之间结合的分子模型。
• Design synthesis and biological evaluation of 3-substituted triazole derivatives
  作者：Bao Gang Wang、Shi Chong Yu、Xiao Yun Chai、Yong Zheng Yan、Hong Gang Hu、Qiu Ye Wu

  DOI：10.1016/j.cclet.2010.11.029

  日期：2011.5

  azole antifungal agents, sixteen 1-(1H-1,2,4-triazole-1-yl)- 2-(2,4-difluorophenyl)-3-(N-n-butyl-N-1-substitutedbenzyl-4-methylene-1H-1,2,3-triazole)-2-propanols have been designed, synthesized and evaluated as antifungal agents. Results of preliminary antifungal tests against eight human pathogenic fungi in vitro showed that some of the compounds exhibited excellent activities with broad spectrum.

  摘要基于吡咯类抗真菌药羊毛甾醇14α-脱甲基酶的活性位点，研究了十六种1-（1H-1,2,4-三唑-1-基）-2-（2,4-二氟苯基）-3-（Nn-已经设计，合成和评估了丁基-N-1-取代的苄基-4-亚甲基-1H-1,2,3-三唑）-2-丙醇作为抗真菌剂。初步针对八种人类病原性真菌的抗真菌试验结果表明，某些化合物具有广谱的优异活性。
• Synthesis and bioactivity evaluation of novel azoles containing dithiocarbamate moieties
  作者：Ben Fu、Maocheng Wu、Lu Huang、Qiuye Wu、Shudong Wang、Xiaoyun Chai

  DOI：10.1007/s00044-017-1948-0

  日期：2017.10

  A series of novel azoles, N-methyl-N-[2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)]-propyl-(1-substituted phenyl)-dithiocarbamate has been designed, synthesized, and screened for antifungal activity by minimum inhibitory concentration. Results of preliminary antifungal tests showed that most of the title compounds had good antifungal activities against nearly all the tested fungal pathogens

  一系列新型唑，N-甲基-N- [2-（2,4-二氟苯基）-2-羟基-3-（1 H -1,2,4-三唑-1-基）]-丙基-（已经设计，合成并通过最小抑制浓度筛选了1-取代的苯基）-二硫代氨基甲酸酯的抗真菌活性。初步的抗真菌试验结果表明，大多数标题化合物对几乎所有测试的真菌病原体，特别是对念珠菌都有良好的抗真菌活性。这项研究最令人惊讶的发现是，化合物4a，4e和4k的抗烟曲霉活性比氟康唑高。