1-(7-(3-chlorophenoxy)heptyl)homopiperidine hydrogen oxalate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(7-(3-chlorophenoxy)heptyl)homopiperidine hydrogen oxalate
• 英文别名: 1-[7-(3-Chlorophenoxy)heptyl]azepane;oxalic acid；1-[7-(3-chlorophenoxy)heptyl]azepane;oxalic acid
• 化学式: C₂H₂O₄*C₁₉H₃₀ClNO
• 分子量: 413.942
• InChiKey: XBHJZQRBUCXAOA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  87.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1,7-二溴庚烷 在 sodium proprionate 、 potassium carbonate 、 potassium iodide 作用下， 以 丙醇 、 乙醇 、 水 为溶剂， 反应 26.25h， 生成 1-(7-(3-chlorophenoxy)heptyl)homopiperidine hydrogen oxalate
  参考文献：
  名称：

  Chlorophenoxy aminoalkyl derivatives as histamine H3R ligands and antiseizure agents

  摘要：

  A series of twenty new chlorophenoxyalkylamine derivatives (9-28) was synthesized and evaluated on their binding properties at the human histamine H-3 receptor (hH(3)R). The spacer alkyl chain contained five to seven carbon atoms. The highest affinities have shown the 4-chloro substituted derivatives 10 and 25 (K-i = 133 and 128 nM, respectively) classified as antagonists in cAMP accumulation assay (EC50 = 72 and 75 nM, respectively). Synthesized compounds were also evaluated for anticonvulsant activity in Antiepileptic Screening Program (ASP) at National Institute of Neurological Disorders and Stroke (USA). Two compounds (4-chloro substituted derivatives: 20 and 26) were the most promising and showed in the MES seizure model in rats (after ip administration) ED50 values of 14 mg/kg and 13.18 mg/kg, respectively. Protective indexes (PI = TD50/ED50) were 3.2 for 20 and 3.8 for 26. Moreover, molecular modeling and docking studies were undertaken to explain affinity at hH(3)R of target compounds, and the experimentally and in silico estimation of properties like lipophilicity and metabolism was performed. Antiproliferative effects have been also investigated in vitro for selected compounds (10 and 25). These compounds neither possessed significant antiproliferative and antitumor activity, nor modulated CYP3A4 activity up to concentration of 10 mu M. (C) 2015 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2015.11.021

文献信息

• Chlorophenoxy aminoalkyl derivatives as histamine H3R ligands and antiseizure agents
  作者：Kamil Kuder、Dorota Łażewska、Gniewomir Latacz、Johannes Stephan Schwed、Tadeusz Karcz、Holger Stark、Janina Karolak-Wojciechowska、Katarzyna Kieć-Kononowicz

  DOI：10.1016/j.bmc.2015.11.021

  日期：2016.1

  A series of twenty new chlorophenoxyalkylamine derivatives (9-28) was synthesized and evaluated on their binding properties at the human histamine H-3 receptor (hH(3)R). The spacer alkyl chain contained five to seven carbon atoms. The highest affinities have shown the 4-chloro substituted derivatives 10 and 25 (K-i = 133 and 128 nM, respectively) classified as antagonists in cAMP accumulation assay (EC50 = 72 and 75 nM, respectively). Synthesized compounds were also evaluated for anticonvulsant activity in Antiepileptic Screening Program (ASP) at National Institute of Neurological Disorders and Stroke (USA). Two compounds (4-chloro substituted derivatives: 20 and 26) were the most promising and showed in the MES seizure model in rats (after ip administration) ED50 values of 14 mg/kg and 13.18 mg/kg, respectively. Protective indexes (PI = TD50/ED50) were 3.2 for 20 and 3.8 for 26. Moreover, molecular modeling and docking studies were undertaken to explain affinity at hH(3)R of target compounds, and the experimentally and in silico estimation of properties like lipophilicity and metabolism was performed. Antiproliferative effects have been also investigated in vitro for selected compounds (10 and 25). These compounds neither possessed significant antiproliferative and antitumor activity, nor modulated CYP3A4 activity up to concentration of 10 mu M. (C) 2015 Published by Elsevier Ltd.