N-[1-(2,4-difluorophenyl)-2-imidazol-1-yl-ethoxy]-1-[4-(2-morpholinoethoxy)phenyl]ethanimine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-[1-(2,4-difluorophenyl)-2-imidazol-1-yl-ethoxy]-1-[4-(2-morpholinoethoxy)phenyl]ethanimine
• 英文别名: (E)-N-[1-(2,4-difluorophenyl)-2-imidazol-1-ylethoxy]-1-[4-(2-morpholin-4-ylethoxy)phenyl]ethanimine
• 化学式: C₂₅H₂₈F₂N₄O₃
• 分子量: 470.519
• InChiKey: HAUKOPVZEIYVBM-VUTHCHCSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  61.1
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-(4-(2-morpholinoethoxy)phenyl)ethanone 、 以 甲醇 为溶剂， 反应 120.0h， 以52%的产率得到N-[1-(2,4-difluorophenyl)-2-imidazol-1-yl-ethoxy]-1-[4-(2-morpholinoethoxy)phenyl]ethanimine
  参考文献：
  名称：

  Synthesis, Antifungal Activity, and Molecular Modeling Studies of New Inverted Oxime Ethers of Oxiconazole

  摘要：

  Some new oxime ethers of types 7 and 8, in which the methyleneaminoxy group, C=N-O, of oxiconazole 6 is in an inverted atomic sequence, were synthesized and tested for their antifungal activities. Among them, the type 7 compounds, such as the N-ethoxy-morpholino-substituted derivatives 71-o (Table 1), showed good antifungal properties against the Candida strains tested, with minimum inhibitory concentration (MIC) values similar to those of the reference drug 6. A remarkable result was obtained with these types of azoles, which had shown a cidal character against Candida albicans, while the reference drug oxiconazole was only fungistatic in the same tests. This fact may be seen from a comparison of the MIC values with those of the minimum fungicidal concentration (MFC) values for most of the type 7 compounds assayed that have shown differences between the MIC and the MFC, which are lower than three double diluitions. A simple molecular modeling of the P450 14-alpha-sterol demethylase from C. albicans (Candida P450DM) was built in order to understand how the structural differences between type 7 compounds and oxiconazole 6 can induce different antifungal profiles. The results of this work seem to confirm that it is possible to reverse the atomic sequence of the methyleneaminoxy group, C=N-O, of 6, obtaining new imidazoles possessing good antifungal properties.

  DOI：

  10.1021/jm020980t

文献信息

• Synthesis, Antifungal Activity, and Molecular Modeling Studies of New Inverted Oxime Ethers of Oxiconazole
  作者：Armando Rossello、Simone Bertini、Annalina Lapucci、Marco Macchia、Adriano Martinelli、Simona Rapposelli、Esperanza Herreros、Bruno Macchia

  DOI：10.1021/jm020980t

  日期：2002.10.1

  Some new oxime ethers of types 7 and 8, in which the methyleneaminoxy group, C=N-O, of oxiconazole 6 is in an inverted atomic sequence, were synthesized and tested for their antifungal activities. Among them, the type 7 compounds, such as the N-ethoxy-morpholino-substituted derivatives 71-o (Table 1), showed good antifungal properties against the Candida strains tested, with minimum inhibitory concentration (MIC) values similar to those of the reference drug 6. A remarkable result was obtained with these types of azoles, which had shown a cidal character against Candida albicans, while the reference drug oxiconazole was only fungistatic in the same tests. This fact may be seen from a comparison of the MIC values with those of the minimum fungicidal concentration (MFC) values for most of the type 7 compounds assayed that have shown differences between the MIC and the MFC, which are lower than three double diluitions. A simple molecular modeling of the P450 14-alpha-sterol demethylase from C. albicans (Candida P450DM) was built in order to understand how the structural differences between type 7 compounds and oxiconazole 6 can induce different antifungal profiles. The results of this work seem to confirm that it is possible to reverse the atomic sequence of the methyleneaminoxy group, C=N-O, of 6, obtaining new imidazoles possessing good antifungal properties.