N-{[3-(cyclopentyloxy)-4-methoxyphenyl]methylene}morpholin-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}morpholin-4-amine
• 英文别名: 1-(3-cyclopentyloxy-4-methoxyphenyl)-N-morpholin-4-ylmethanimine
• 化学式: C₁₇H₂₄N₂O₃
• 分子量: 304.389
• InChiKey: GHGFTLOVVTXFHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  43.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-{[3-(cyclopentyloxy)-4-methoxyphenyl]methylene}morpholin-4-amine 在 盐酸 、 sodium cyanoborohydride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 12.0h， 生成 N-[(3-cyclopentyloxy-4-methoxyphenyl)methyl]morpholin-4-amine
  参考文献：
  名称：

  Synthesis and biological evaluation of neutrophilic inflammation inhibitors

  摘要：

  In several non-infectious human diseases, such as ulcerous colitis, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), the extravasal recruitment of neutrophils plays a crucial role in the development of tissue damage, which, when persistent, can lead to the irreversible organ dysfunction. The neutrophil activation is controlled by a number of intracellular pathways, particularly by a cAMP-dependent protein kinase A (PKA) which also acts on phosphodiesterase IV (PDE4) gene stimulating the synthesis of this enzyme, able to transform cAMP to inactive AMP. PDE4 inhibitors enhance intracellular cAMP and decrease inflammatory cell activation. Several 3-cyclopentyloxy-4-methoxybenzaldehyde and 3-cyclopentyloxy-4-methoxybenzoic acid derivatives were synthesized and studied by us to evaluate their ability to inhibit the superoxide anion production in human neutrophils. These compounds were found able to inhibit the neutrophil activation and some of them increased the cAMP level on tumor necrosis factor-alpha-stimulated neutrophils. Moreover, they also inhibited selectively the human PDE4 enzyme, although they are less potent than the reference compound Rolipram. We report here synthesis, biological studies and some SAR considerations concerning the above mentioned compounds.

  DOI：

  10.1016/j.farmac.2003.08.005
• 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}morpholin-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 and biological evaluation of neutrophilic inflammation inhibitors
  作者：Olga Bruno、Chiara Brullo、Nicoletta Arduino、Silvia Schenone、Angelo Ranise、Francesco Bondavalli、Luciano Ottonello、Patrizia Dapino、Franco Dallegri

  DOI：10.1016/j.farmac.2003.08.005

  日期：2004.3

  In several non-infectious human diseases, such as ulcerous colitis, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), the extravasal recruitment of neutrophils plays a crucial role in the development of tissue damage, which, when persistent, can lead to the irreversible organ dysfunction. The neutrophil activation is controlled by a number of intracellular pathways, particularly by a cAMP-dependent protein kinase A (PKA) which also acts on phosphodiesterase IV (PDE4) gene stimulating the synthesis of this enzyme, able to transform cAMP to inactive AMP. PDE4 inhibitors enhance intracellular cAMP and decrease inflammatory cell activation. Several 3-cyclopentyloxy-4-methoxybenzaldehyde and 3-cyclopentyloxy-4-methoxybenzoic acid derivatives were synthesized and studied by us to evaluate their ability to inhibit the superoxide anion production in human neutrophils. These compounds were found able to inhibit the neutrophil activation and some of them increased the cAMP level on tumor necrosis factor-alpha-stimulated neutrophils. Moreover, they also inhibited selectively the human PDE4 enzyme, although they are less potent than the reference compound Rolipram. We report here synthesis, biological studies and some SAR considerations concerning the above mentioned compounds.
• 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.