N-(2-(3-(4-(3-hydroxyphenoxy)butoxy)phenyl)(methyl)aminoethyl)acetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-(2-(3-(4-(3-hydroxyphenoxy)butoxy)phenyl)(methyl)aminoethyl)acetamide
• 英文别名: N-[2-[3-[4-(3-hydroxyphenoxy)butoxy]-N-methylanilino]ethyl]acetamide
• 化学式: C₂₁H₂₈N₂O₄
• 分子量: 372.464
• InChiKey: PVNJRXRFOJWZIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  71
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(2-(3-(4-(3-hydroxyphenoxy)butoxy)phenyl)(methyl)aminoethyl)acetamide 、 环己基异氰酸酯 在 三乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 18.0h， 以65%的产率得到(3-(4-{3-[(2-acetamidoethyl)methylamino]phenoxy}butyloxy)phenyl)-N-cyclohexylcarbamate
  参考文献：
  名称：

  Identification of Bivalent Ligands with Melatonin Receptor Agonist and Fatty Acid Amide Hydrolase (FAAH) Inhibitory Activity That Exhibit Ocular Hypotensive Effect in the Rabbit

  摘要：

  Activation of melatonin receptors and inhibition of fatty acid amide hydrolase (FAAH) have both shown potential benefits for the treatment of glaucoma. To exploit the combination of these biological activities in single therapeutic agents, we designed dual-acting compounds sharing the pharmacophore elements required for the two targets, in search for balanced potencies as MT1/MT2 agonists and FAAH inhibitors. In particular, the N-anilinoethylamide scaffold, previously developed for melatonergic ligands, was decorated at meta position with a polymethylene linker bound to an O-arylcarbamate group, substituted according to known structure-activity relationships for FAAH inhibition. For the most active series, the N-anilinoethylamide portion was also replaced with the indole scaffold of melatonin. O-Biphenyl-3-ylcarbamate characterized by remarkable and balanced activity at both targets, in the nanomolar range for compound 29. Topical administration reduced elevated intraocular pressure in rabbits, with a longer action and improved efficacy compared to the reference compounds melatonin and URB597.

  DOI：

  10.1021/acs.jmedchem.8b00893
• 作为产物：
  描述：

  N-[2-[(3-羟基苯基)甲基氨基]乙基]-乙酰胺 在 palladium 10% on activated carbon 、 氢气 、 sodium hydride 作用下， 以 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， -10.0~20.0 ℃ 、101.33 kPa 条件下， 反应 32.17h， 生成 N-(2-(3-(4-(3-hydroxyphenoxy)butoxy)phenyl)(methyl)aminoethyl)acetamide
  参考文献：
  名称：

  Identification of Bivalent Ligands with Melatonin Receptor Agonist and Fatty Acid Amide Hydrolase (FAAH) Inhibitory Activity That Exhibit Ocular Hypotensive Effect in the Rabbit

  摘要：

  Activation of melatonin receptors and inhibition of fatty acid amide hydrolase (FAAH) have both shown potential benefits for the treatment of glaucoma. To exploit the combination of these biological activities in single therapeutic agents, we designed dual-acting compounds sharing the pharmacophore elements required for the two targets, in search for balanced potencies as MT1/MT2 agonists and FAAH inhibitors. In particular, the N-anilinoethylamide scaffold, previously developed for melatonergic ligands, was decorated at meta position with a polymethylene linker bound to an O-arylcarbamate group, substituted according to known structure-activity relationships for FAAH inhibition. For the most active series, the N-anilinoethylamide portion was also replaced with the indole scaffold of melatonin. O-Biphenyl-3-ylcarbamate characterized by remarkable and balanced activity at both targets, in the nanomolar range for compound 29. Topical administration reduced elevated intraocular pressure in rabbits, with a longer action and improved efficacy compared to the reference compounds melatonin and URB597.

  DOI：

  10.1021/acs.jmedchem.8b00893