2-Heptyl-7-hydroxy-2-methyl-chroman-4-one | 282733-02-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2-Heptyl-7-hydroxy-2-methyl-chroman-4-one
• 英文别名: 2-Heptyl-7-hydroxy-2-methylchroman-4-one；2-heptyl-7-hydroxy-2-methyl-3H-chromen-4-one
• CAS: 282733-02-2
• 化学式: C₁₇H₂₄O₃
• 分子量: 276.376
• InChiKey: NGNJBJKCBBENBL-UHFFFAOYSA-N

物化性质

• 沸点：
  425.4±45.0 °C(Predicted)
• 密度：
  1.059±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-Heptyl-7-hydroxy-2-methyl-chroman-4-one 在 盐酸 、 sodium tetrahydroborate 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 为溶剂， 反应 28.0h， 生成 2-Heptyl-7-methoxy-2-methyl-2H-chromene
  参考文献：
  名称：

  Structure-Based de Novo Design, Synthesis, and Biological Evaluation of Non-Azole Inhibitors Specific for Lanosterol 14α-Demethylase of Fungi

  摘要：

  The active site of lanosterol 14alpha-demethylase (CYP51) was investigated via MCSS functional group mapping and LUDI calculations. Several non-azole lead molecules were obtained by coupling structure-based de novo design with chemical synthesis and biological evaluation. All of the lead molecules exhibited a strong inhibitory effect on CYP51 of Candida albicans. They occupy the substrate-binding site and interfere with the binding of azole antifungal agents in a competitive manner. The mode of action of the lead molecules was validated by spectrophotomeric analysis and SAR studies. This is the first successful example reported for the inhibitor design of the cytochrome P450 superfamily using the de novo design strategy. Because the affinity of the lead molecules for CYP51 was mainly attributed to their nonbonding interaction with the apoprotein, the studies presented here afford the opportunity to develop novel antifungal agents that specifically interact with the residues in the active site and avoid the serious toxicity arising from coordination binding with the heme of mammalian P450s.

  DOI：

  10.1021/jm020362c
• 作为产物：
  描述：

  2,4-二羟基苯乙酮 、 2-壬酮 在 四氢吡咯 、 3 A molecular sieve 作用下， 以 乙醇 为溶剂， 以62.31%的产率得到2-Heptyl-7-hydroxy-2-methyl-chroman-4-one
  参考文献：
  名称：

  Structure-Based de Novo Design, Synthesis, and Biological Evaluation of Non-Azole Inhibitors Specific for Lanosterol 14α-Demethylase of Fungi

  摘要：

  The active site of lanosterol 14alpha-demethylase (CYP51) was investigated via MCSS functional group mapping and LUDI calculations. Several non-azole lead molecules were obtained by coupling structure-based de novo design with chemical synthesis and biological evaluation. All of the lead molecules exhibited a strong inhibitory effect on CYP51 of Candida albicans. They occupy the substrate-binding site and interfere with the binding of azole antifungal agents in a competitive manner. The mode of action of the lead molecules was validated by spectrophotomeric analysis and SAR studies. This is the first successful example reported for the inhibitor design of the cytochrome P450 superfamily using the de novo design strategy. Because the affinity of the lead molecules for CYP51 was mainly attributed to their nonbonding interaction with the apoprotein, the studies presented here afford the opportunity to develop novel antifungal agents that specifically interact with the residues in the active site and avoid the serious toxicity arising from coordination binding with the heme of mammalian P450s.

  DOI：

  10.1021/jm020362c

文献信息

• Structure-Based de Novo Design, Synthesis, and Biological Evaluation of Non-Azole Inhibitors Specific for Lanosterol 14α-Demethylase of Fungi
  作者：Haitao Ji、Wannian Zhang、Min Zhang、Makiko Kudo、Yuri Aoyama、Yuzo Yoshida、Chunquan Sheng、Yunlong Song、Song Yang、Youjun Zhou、Jiaguo Lü、Jü Zhu

  DOI：10.1021/jm020362c

  日期：2003.2.1

  The active site of lanosterol 14alpha-demethylase (CYP51) was investigated via MCSS functional group mapping and LUDI calculations. Several non-azole lead molecules were obtained by coupling structure-based de novo design with chemical synthesis and biological evaluation. All of the lead molecules exhibited a strong inhibitory effect on CYP51 of Candida albicans. They occupy the substrate-binding site and interfere with the binding of azole antifungal agents in a competitive manner. The mode of action of the lead molecules was validated by spectrophotomeric analysis and SAR studies. This is the first successful example reported for the inhibitor design of the cytochrome P450 superfamily using the de novo design strategy. Because the affinity of the lead molecules for CYP51 was mainly attributed to their nonbonding interaction with the apoprotein, the studies presented here afford the opportunity to develop novel antifungal agents that specifically interact with the residues in the active site and avoid the serious toxicity arising from coordination binding with the heme of mammalian P450s.