methyl-{4-[5-oxo-1-(4-trifluoromethylbenzyl)-1,5-dihydro-[1,2,4]triazol-4-yl]benzyl}carbamic acid tert-butyl ester | 887139-27-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl-{4-[5-oxo-1-(4-trifluoromethylbenzyl)-1,5-dihydro-[1,2,4]triazol-4-yl]benzyl}carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-methyl-N-[[4-[5-oxo-1-[[4-(trifluoromethyl)phenyl]methyl]-1,2,4-triazol-4-yl]phenyl]methyl]carbamate
• CAS: 887139-27-7
• 化学式: C₂₃H₂₅F₃N₄O₃
• 分子量: 462.472
• InChiKey: WTEFJICJKUFHSM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  65.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl-{4-[5-oxo-1-(4-trifluoromethylbenzyl)-1,5-dihydro-[1,2,4]triazol-4-yl]benzyl}carbamic acid tert-butyl ester 在 盐酸 、 三乙胺 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 32.0h， 生成 4-[4-({[2-(2,4-Difluoro-phenyl)-2-hydroxy-3-[1,2,4]triazol-1-yl-propyl]-methyl-amino}-methyl)-phenyl]-2-(4-trifluoromethyl-benzyl)-2,4-dihydro-[1,2,4]triazol-3-one
  参考文献：
  名称：

  Structure-Based Optimization of Azole Antifungal Agents by CoMFA, CoMSIA, and Molecular Docking

  摘要：

  In a continuing effort to develop highly potent azole antifungal agents, the three-dimensional quantitative structure-activity relationship methods. CoMFA and CoMSIA, were applied using a set of novel azole antifungal compounds. The binding mode of the compounds at the active site of lanosterol 14 alpha-demethylase was further explored using the flexible docking method. Various hydrophobic, van der Waals,pi-pi stacking, and hydrogen bonding interactions were observed between the azoles and the enzyme. Based on results from the molecular modeling, a receptor-based pharmacophore model was established to guide the rational optimization of the azole antifungal agents. Thus, a total of 57 novel azoles were designed and synthesized by a three-step optimization process. In vitro antifungal assay revealed that the antifungal activities of these novel azoles were greatly improved, which confirmed the reliability of the model from molecular modeling.

  DOI：

  10.1021/jm051211n
• 作为产物：
  描述：

  methyl-[4-(5-oxo-1,5-dihydro-[1,2,4]triazol-4-yl)benzyl]carbamic acid tert-butyl ester 、 4-(三氟甲基)苄基氯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以78.3%的产率得到methyl-{4-[5-oxo-1-(4-trifluoromethylbenzyl)-1,5-dihydro-[1,2,4]triazol-4-yl]benzyl}carbamic acid tert-butyl ester
  参考文献：
  名称：

  Structure-Based Optimization of Azole Antifungal Agents by CoMFA, CoMSIA, and Molecular Docking

  摘要：

  In a continuing effort to develop highly potent azole antifungal agents, the three-dimensional quantitative structure-activity relationship methods. CoMFA and CoMSIA, were applied using a set of novel azole antifungal compounds. The binding mode of the compounds at the active site of lanosterol 14 alpha-demethylase was further explored using the flexible docking method. Various hydrophobic, van der Waals,pi-pi stacking, and hydrogen bonding interactions were observed between the azoles and the enzyme. Based on results from the molecular modeling, a receptor-based pharmacophore model was established to guide the rational optimization of the azole antifungal agents. Thus, a total of 57 novel azoles were designed and synthesized by a three-step optimization process. In vitro antifungal assay revealed that the antifungal activities of these novel azoles were greatly improved, which confirmed the reliability of the model from molecular modeling.

  DOI：

  10.1021/jm051211n

文献信息

• Structure-Based Optimization of Azole Antifungal Agents by CoMFA, CoMSIA, and Molecular Docking
  作者：Chunquan Sheng、Wannian Zhang、Haitao Ji、Min Zhang、Yunlong Song、Hui Xu、Jie Zhu、Zhenyuan Miao、Qingfen Jiang、Jianzhong Yao、Youjun Zhou、Jü Zhu、Jiaguo Lü

  DOI：10.1021/jm051211n

  日期：2006.4.1

  In a continuing effort to develop highly potent azole antifungal agents, the three-dimensional quantitative structure-activity relationship methods. CoMFA and CoMSIA, were applied using a set of novel azole antifungal compounds. The binding mode of the compounds at the active site of lanosterol 14 alpha-demethylase was further explored using the flexible docking method. Various hydrophobic, van der Waals,pi-pi stacking, and hydrogen bonding interactions were observed between the azoles and the enzyme. Based on results from the molecular modeling, a receptor-based pharmacophore model was established to guide the rational optimization of the azole antifungal agents. Thus, a total of 57 novel azoles were designed and synthesized by a three-step optimization process. In vitro antifungal assay revealed that the antifungal activities of these novel azoles were greatly improved, which confirmed the reliability of the model from molecular modeling.