1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[4-(2-fluoro-4-aminophenyl)piperazin-1-yl]propan-2-ol | 950821-44-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[4-(2-fluoro-4-aminophenyl)piperazin-1-yl]propan-2-ol
• 英文别名: 2-(2,4-difluorophenyl)-1-[4-(2-fluoro-4-amino-phenyl)-piperazin-1-yl]-3-(1H-1,2,4-triazol-1-yl)-propan-2-ol；1-[4-(4-Amino-2-fluoro-phenyl)piperazin-1-yl]-2-(2,4-difluorophenyl)-3-(1,2,4-triazol-1-yl)propan-2-ol；1-[4-(4-amino-2-fluorophenyl)piperazin-1-yl]-2-(2,4-difluorophenyl)-3-(1,2,4-triazol-1-yl)propan-2-ol
• CAS: 950821-44-0
• 化学式: C₂₁H₂₃F₃N₆O
• 分子量: 432.448
• InChiKey: SPCWTIBUVSFKRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  83.4
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[4-(2-fluoro-4-aminophenyl)piperazin-1-yl]propan-2-ol 、 4-异丙基苯甲酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以71.8%的产率得到N-[4-[4-[2-(2,4-difluorophenyl)-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]piperazin-1-yl]-3-fluoro-phenyl]-4-isopropyl-benzamide
  参考文献：
  名称：

  Synthesis of novel triazole derivatives as inhibitors of cytochrome P450 14α-demethylase (CYP51)

  摘要：

  A series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl]-propan-2-ols have been designed and synthesized on the basis of the structure-activity relationships and antimycotic mechanism of azole antifungal agents. Their structures were confirmed by elemental analysis, IR, MS and H-1 NMR. Results of preliminary antifungal tests against eight human pathogenic fungi (Candida albicans, Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans; Aspergillus fumigatus, Trichophyton rubrum, Fonsecaea compacta, and Microsporum gypseum) in vitro showed that all title compounds exhibited activity against fungi tested to some extent. Among the compounds tested, all compounds showed higher activity against C. albicans than fluconazole in vitro. Compounds 3, 6-8, 28, 29, and 32 exhibited the same activities against C. albicans as voriconazole (with the MIC value of 0.0152 mu g/mL). Compounds 3, 6, and 7 showed higher activity against C. parapsilosis than all five positive controls. (c) 2007 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2007.01.006
• 作为产物：
  描述：

  1-(2-氟-4-硝基苯基)哌嗪 在 一水合肼 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 8.5h， 生成 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[4-(2-fluoro-4-aminophenyl)piperazin-1-yl]propan-2-ol
  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

文献信息

• 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。
• Synthesis and evaluation of novel 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl]-propan-2-ols as antifungal agents
  作者：Qing-Yan Sun、Wan-Nian Zhang、Jian-Ming Xu、Yong-Bing Cao、Qiu-Ye Wu、Da-Zhi Zhang、Chao-Mei Liu、Shi-Chong Yu、Yuan-Ying Jiang

  DOI：10.1016/j.ejmech.2006.11.003

  日期：2007.8

  A series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl]-prop n-2-ols have been designed and synthesized on the basis of the structure-activity relationships and antimycotic mechanism of azole antifungal agents. Their structutes were confirmed by elemental analysis, IR, MS, H-1 NMR and 13 C NMR. Results of preliminary antifungal tests against six human pathogenic fungi (Candida albicans, Candida parapsilosis, Cryptococcus neoformans, Candida tropicalis, inherently fluconazole-resistant Candida krusei, Candida glabrata) in vitro showed that all title compounds exhibited activity against fungi tested to some extent except against C. tropicalis. Compound 5b showed higher activity against C. albicans, C. parapsilosis and C. krusei than fluconazole, and its MIC values were determined to be 0.5 mu g/mL, 1 mu g/mL and 4 mu g/mL, respectively. Compound 5k showed higher activities against Torulopsis glabrata than fluconazole (with the MIC value of 2 mu g/mL). Compounds 5a, 5c, 5f, 5g, 5i exhibited higher activities against C. parapsilosis than fluconazole (with the MIC. values of 2 mu g/mL, 2 mu g/mL, 2 mu g/mL, 1 mu g/mL and 2 mu g/mL, respectively). (c) 2006 Elsevier Masson SAS. All rights reserved.
• Synthesis of novel triazole derivatives as inhibitors of cytochrome P450 14α-demethylase (CYP51)
  作者：Qing-Yan Sun、Jian-Ming Xu、Yong-Bing Cao、Wan-Nian Zhang、Qiu-Ye Wu、Da-Zhi Zhang、Jun Zhang、Hui-Qing Zhao、Yuan-Ying Jiang

  DOI：10.1016/j.ejmech.2007.01.006

  日期：2007.9

  A series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl]-propan-2-ols have been designed and synthesized on the basis of the structure-activity relationships and antimycotic mechanism of azole antifungal agents. Their structures were confirmed by elemental analysis, IR, MS and H-1 NMR. Results of preliminary antifungal tests against eight human pathogenic fungi (Candida albicans, Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans; Aspergillus fumigatus, Trichophyton rubrum, Fonsecaea compacta, and Microsporum gypseum) in vitro showed that all title compounds exhibited activity against fungi tested to some extent. Among the compounds tested, all compounds showed higher activity against C. albicans than fluconazole in vitro. Compounds 3, 6-8, 28, 29, and 32 exhibited the same activities against C. albicans as voriconazole (with the MIC value of 0.0152 mu g/mL). Compounds 3, 6, and 7 showed higher activity against C. parapsilosis than all five positive controls. (c) 2007 Elsevier Masson SAS. All rights reserved.
• Design, synthesis and antifungal activities of novel 1,2,4-triazole derivatives
  作者：Jianming Xu、Yongbing Cao、Jun Zhang、Shichong Yu、Yan Zou、Xiaoyun Chai、Qiuye Wu、Dazhi Zhang、Yuanying Jiang、Qingyan Sun

  DOI：10.1016/j.ejmech.2011.02.042

  日期：2011.7

  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.