3-(cyclopentyloxy)-4-methoxy-N-(4-methoxybenzyl)benzamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(cyclopentyloxy)-4-methoxy-N-(4-methoxybenzyl)benzamide
• 英文别名: 3-cyclopentyloxy-4-methoxy-N-[(4-methoxyphenyl)methyl]benzamide
• 化学式: C₂₁H₂₅NO₄
• 分子量: 355.434
• InChiKey: SEHLBLBZRVSJRM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  56.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-羟基-4-甲氧基苯甲酸甲酯 在 氯化亚砜 、 caesium carbonate 、 三乙胺 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 3-(cyclopentyloxy)-4-methoxy-N-(4-methoxybenzyl)benzamide
  参考文献：
  名称：

  Catecholic amides as potential selective phosphodiesterase 4D inhibitors: Design, synthesis, pharmacological evaluation and structure–activity relationships

  摘要：

  In this study, a series of catechol-based amides (8a-n) with different amide linkers linking the catecholic moiety to the terminal phenyl ring was designed and synthesized as potent phosphodiesterase (PDE) 4D inhibitors. The inhibitory activities of these compounds were evaluated against the core catalytic domains of human PDE4 (PDE4CAT), full-length PDE4B1 and PDE4D7 enzymes, and other PDE family members. The results indicated the majority of compounds 8a-n displayed moderate to good inhibitory activities against PDE4CAT. Among these compounds, compound 8j with a short amide linker (ACONHCH2A) displayed comparable PDE4CAT inhibitory activity (IC50 = 410 nM) with rolipram. More interestingly, compound 8g, a potent and selective PDE4D inhibitor (IC50 = 94 nM), exhibited a 10-fold selectivity over the PDE4B subtypes and an over 1000-fold selectivity against other PDE family members. Docking simulations suggested that 8g forms three extra H-bonds with the NAH of residue Asn487 and two water molecules. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.10.033

文献信息

• Catecholic amides as potential selective phosphodiesterase 4D inhibitors: Design, synthesis, pharmacological evaluation and structure–activity relationships
  作者：Zhong-Zhen Zhou、Bing-Chen Ge、Yu-Fang Chen、Xiu-Dong Shi、Xue-Mei Yang、Jiang-Ping Xu

  DOI：10.1016/j.bmc.2015.10.033

  日期：2015.11

  In this study, a series of catechol-based amides (8a-n) with different amide linkers linking the catecholic moiety to the terminal phenyl ring was designed and synthesized as potent phosphodiesterase (PDE) 4D inhibitors. The inhibitory activities of these compounds were evaluated against the core catalytic domains of human PDE4 (PDE4CAT), full-length PDE4B1 and PDE4D7 enzymes, and other PDE family members. The results indicated the majority of compounds 8a-n displayed moderate to good inhibitory activities against PDE4CAT. Among these compounds, compound 8j with a short amide linker (ACONHCH2A) displayed comparable PDE4CAT inhibitory activity (IC50 = 410 nM) with rolipram. More interestingly, compound 8g, a potent and selective PDE4D inhibitor (IC50 = 94 nM), exhibited a 10-fold selectivity over the PDE4B subtypes and an over 1000-fold selectivity against other PDE family members. Docking simulations suggested that 8g forms three extra H-bonds with the NAH of residue Asn487 and two water molecules. (C) 2015 Elsevier Ltd. All rights reserved.