2-(hexahydro-1H-azepin-1-yl)ethyl phenyl-3-thienylethanoate | 14176-07-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环庚烷
• 英文名称: 2-(hexahydro-1H-azepin-1-yl)ethyl phenyl-3-thienylethanoate
• 英文别名: 2-(Azepan-1-yl)ethyl 2-phenyl-2-thiophen-3-ylacetate
• CAS: 14176-07-9
• 化学式: C₂₀H₂₅NO₂S
• 分子量: 343.49
• InChiKey: KSLPMGPWGNSRTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  57.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-Thienylphenylessigsaeure 、 2-(环己亚氨基)乙基氯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-(hexahydro-1H-azepin-1-yl)ethyl phenyl-3-thienylethanoate
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Cetiedil Analogues as Blockers of the Ca²⁺-Activated K⁺ Permeability of Erythrocytes

  摘要：

  Cetiedil, [2-cyclohexyl-2-(3-thienyl)ethanoic acid 2-(hexahydro-1H-azepin-1-yl)ethyl ester], which blocks the intermediate calcium-activated potassium ion permeability (IKCa) in red blood cells, was used as a lead for investigating structure-activity relationships with the aim of determining the pharmacophore and of synthesizing agents of greater potency. A series of compounds having structures related to cetiedil was made and tested on rabbit erythrocytes. Channel blocking activity within the series was found to correlate well with octanol-water partition coefficients but not with the specific chemical structure of the acid moiety. However, whereas log P for the compounds spans a range of values over 4 orders of magnitude, potency only increases by 2 orders. This suggests that hydrophobic interactions with an active site on the channel are probably not the main determinants of activity. It seems more likely that increased lipophilicity enhances access to the channel, probably from within the cell membrane. In keeping with this interpretation, cetiedil methoiodide was found to be inactive, Triphenylethanoic was found to be a more effective acid grouping than 2-cyclohexyl-2-(3-thienyl)ethanoic, and its 2-(hexahydro-1H-azepin-l-yl)ethyl ester (11) was approximately 3 times more potent than cetiedil. The 9-benzylfluoren-9-yl carboxylic acid ester (21) was found to be approximately 9 times more active than cetiedil, and replacing -CO2- in 21 by an ethynyl (-C dropC-) linkage (compound 26, UCL 1608) increased potency by some 15-fold over that of cetiedil.

  DOI：

  10.1021/jm001113w

文献信息

• Synthesis and Structure−Activity Relationships of Cetiedil Analogues as Blockers of the Ca²⁺-Activated K⁺ Permeability of Erythrocytes
  作者：Craig J. Roxburgh、C. Robin Ganellin、Salah Athmani、Alessandra Bisi、Wilma Quaglia、David C. H. Benton、Mark A. R. Shiner、Misbah Malik-Hall、Dennis G. Haylett、Donald H. Jenkinson

  DOI：10.1021/jm001113w

  日期：2001.9.1

  Cetiedil, [2-cyclohexyl-2-(3-thienyl)ethanoic acid 2-(hexahydro-1H-azepin-1-yl)ethyl ester], which blocks the intermediate calcium-activated potassium ion permeability (IKCa) in red blood cells, was used as a lead for investigating structure-activity relationships with the aim of determining the pharmacophore and of synthesizing agents of greater potency. A series of compounds having structures related to cetiedil was made and tested on rabbit erythrocytes. Channel blocking activity within the series was found to correlate well with octanol-water partition coefficients but not with the specific chemical structure of the acid moiety. However, whereas log P for the compounds spans a range of values over 4 orders of magnitude, potency only increases by 2 orders. This suggests that hydrophobic interactions with an active site on the channel are probably not the main determinants of activity. It seems more likely that increased lipophilicity enhances access to the channel, probably from within the cell membrane. In keeping with this interpretation, cetiedil methoiodide was found to be inactive, Triphenylethanoic was found to be a more effective acid grouping than 2-cyclohexyl-2-(3-thienyl)ethanoic, and its 2-(hexahydro-1H-azepin-l-yl)ethyl ester (11) was approximately 3 times more potent than cetiedil. The 9-benzylfluoren-9-yl carboxylic acid ester (21) was found to be approximately 9 times more active than cetiedil, and replacing -CO2- in 21 by an ethynyl (-C dropC-) linkage (compound 26, UCL 1608) increased potency by some 15-fold over that of cetiedil.