3-(cyclopentyloxy)-4-methoxybenzaldehyde O-[2-(2,6-dimethylmorpholin-4-yl)-2-oxoethyl]oxime

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(cyclopentyloxy)-4-methoxybenzaldehyde O-[2-(2,6-dimethylmorpholin-4-yl)-2-oxoethyl]oxime
• 英文别名: 3-(cyclopentyloxy)-4-methoxybenzaldehyde O-(2-(2,6-dimethylmorpholino)-2-oxoethyl) oxime；2-[(3-Cyclopentyloxy-4-methoxyphenyl)methylideneamino]oxy-1-(2,6-dimethylmorpholin-4-yl)ethanone；2-[(3-cyclopentyloxy-4-methoxyphenyl)methylideneamino]oxy-1-(2,6-dimethylmorpholin-4-yl)ethanone
• 化学式: C₂₁H₃₀N₂O₅
• 分子量: 390.48
• InChiKey: JEXHQZPMUKFOIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  69.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-环戊氧-4-甲氧基苯甲醛 在 盐酸羟胺 、 碳酸氢钠 、 potassium carbonate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 3-(cyclopentyloxy)-4-methoxybenzaldehyde O-[2-(2,6-dimethylmorpholin-4-yl)-2-oxoethyl]oxime
  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

• New Selective Phosphodiesterase 4D Inhibitors Differently Acting on Long, Short, and Supershort Isoforms
  作者：Olga Bruno、Alessia Romussi、Andrea Spallarossa、Chiara Brullo、Silvia Schenone、Francesco Bondavalli、Nicolas Vanthuyne、Christian Roussel

  DOI：10.1021/jm900977c

  日期：2009.11.12

  The lack of selective inhibitors toward the long, short, or supershort phosphodiesterases (PDE4s) prevented researchers from carefully defining the connection between different enzyme isoforms, their brain localization, and their role in neurodegenerative diseases such as Alzheimer's disease (AD). In the search for new therapeutic agents for treating memory and learning disorders, we synthesized new rolipram related PDE4 inhibitors, which had sonic selectivity toward the long form PDE4D3. The first series was synthesized as racemate and then resolved by semipreparative HPLC on chiral supports. Herein we report the synthetic pathways to obtain compounds 1a-c, 2a-c, 3a-c, 4a-f, 5a,b, 6a,b, 7a,b, the chiral analytical study to resolve compounds la-c, 2a-c, 3a-c, the molecular docking Study for compound 1c, and the biological results and sonic SAR considerations that provide sonic insights and hints for the structural requirements for PDE4D Subtype selectivity and enzyme inhibition.
• 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.