N-{[3-(cyclopentyloxy)-4-methoxyphenyl]methylene}-2,6-dimethylmorpholin-4-amine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-{[3-(cyclopentyloxy)-4-methoxyphenyl]methylene}-2,6-dimethylmorpholin-4-amine
• 化学式: C₁₉H₂₈N₂O₃
• 分子量: 332.443
• InChiKey: NDQMTNKRDQKQQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.46
• 重原子数：
  24.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  43.29
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  异香兰素 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 32.0h， 生成 N-{[3-(cyclopentyloxy)-4-methoxyphenyl]methylene}-2,6-dimethylmorpholin-4-amine
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Molecular Modeling of New 3-(Cyclopentyloxy)-4-methoxybenzaldehyde O-(2-(2,6-Dimethylmorpholino)-2-oxoethyl) Oxime (GEBR-7b) Related Phosphodiesterase 4D (PDE4D) Inhibitors

  摘要：

  A new series of 3-(cyclopentyloxy)-4-methoxyphenyl derivatives, structurally related to our hit GEBR-4a (1) and GEBR-7b (2), has been designed by changing length and functionality of the chain linking the catecholic moiety to the terminal cycloamine portion. Among the numerous molecules synthesized, compounds 8, 10a, and 10b showed increased potency as PDE4D enzyme inhibitors with respect to 2 and a good selectivity against PDE4A4, PDE4B2, and PDE4C2 enzymes, without both cytotoxic and genotoxic effects. The ability to enhance cAMP level in neuronal cells was assessed for compound 8. SAR considerations, also confirmed by in silico docking simulations, evidenced that both chain and amino terminal function characterized by higher hydrophilicity are required for a good and selective inhibitor-catalytic pocket interaction.

  DOI：

  10.1021/jm500855w

文献信息

• Synthesis, Biological Evaluation, and Molecular Modeling of New 3-(Cyclopentyloxy)-4-methoxybenzaldehyde <i>O</i>-(2-(2,6-Dimethylmorpholino)-2-oxoethyl) Oxime (GEBR-7b) Related Phosphodiesterase 4D (PDE4D) Inhibitors
  作者：Chiara Brullo、Matteo Massa、Massimo Rocca、Chiara Rotolo、Sara Guariento、Daniela Rivera、Roberta Ricciarelli、Ernesto Fedele、Paola Fossa、Olga Bruno

  DOI：10.1021/jm500855w

  日期：2014.8.28

  A new series of 3-(cyclopentyloxy)-4-methoxyphenyl derivatives, structurally related to our hit GEBR-4a (1) and GEBR-7b (2), has been designed by changing length and functionality of the chain linking the catecholic moiety to the terminal cycloamine portion. Among the numerous molecules synthesized, compounds 8, 10a, and 10b showed increased potency as PDE4D enzyme inhibitors with respect to 2 and a good selectivity against PDE4A4, PDE4B2, and PDE4C2 enzymes, without both cytotoxic and genotoxic effects. The ability to enhance cAMP level in neuronal cells was assessed for compound 8. SAR considerations, also confirmed by in silico docking simulations, evidenced that both chain and amino terminal function characterized by higher hydrophilicity are required for a good and selective inhibitor-catalytic pocket interaction.