1-(2-fluorophenyl)-4-(2-(4-(4-fluorophenyl)piperazin-1-yl)ethyl)piperazine | 51299-26-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-(2-fluorophenyl)-4-(2-(4-(4-fluorophenyl)piperazin-1-yl)ethyl)piperazine
• 英文别名: (o-Fluorphenyl-4-piperazinyl-1)-1-(p-fluorphenyl-4-piperazinyl-1)-1,2-ethan；4-(2-fluoro-phenyl)-4'-(4-fluoro-phenyl)-1,1'-ethane-1,2-diyl-bis-piperazine；1-(2-Fluorophenyl)-4-[2-[4-(4-fluorophenyl)piperazin-1-yl]ethyl]piperazine；1-(2-fluorophenyl)-4-[2-[4-(4-fluorophenyl)piperazin-1-yl]ethyl]piperazine
• CAS: 51299-26-4
• 化学式: C₂₂H₂₈F₂N₄
• 分子量: 386.488
• InChiKey: OJZVNEVUFLMWTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  13
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(4-氟苯基)哌嗪 在 potassium carbonate 、 三乙胺 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 9.5h， 生成 1-(2-fluorophenyl)-4-(2-(4-(4-fluorophenyl)piperazin-1-yl)ethyl)piperazine
  参考文献：
  名称：

  Novel aryl piperazines for alleviation of ‘andropause’ associated prostatic disorders and depression

  摘要：

  A series of seventeen piperazine derivatives have been synthesized and biologically evaluated for the management of andropause-associated prostatic disorders and depression. Five compounds 16,19, 20, 21 and 22 significantly inhibited proliferation of androgen-sensitive LNCaP prostatic cell line with EC50 values of 12.4 mu M, 15.6 11.8 mu M, 10.4 mu M, 12.2 mu M respectively and decreased Ca2+ entry through adrenergic-receptor alpha(1A) blocking activity. Anti-androgenic behaviour of compound 19 and 22 was evident by decreased luciferase activity. The high EC50 value in AR-negative cells PC3 and DU145 suggested that the cytotoxicity of compounds was due to AR down regulation. Compound 19 reduced the prostate weight of rats by 53.8%. Further, forced-swimming and tail-suspension tests revealed antidepressant-like activity of compound 19, lacking effects on neuromuscular co-ordination. In silico ADMET predictions revealed that the compound 19 had good oral absorption, aqueous solubility, non-hepatotoxic and good affinity for plasma protein binding. Pharmacokinetic and tissue uptake of 19 at 10 mg/kg demonstrated an oral bioavailability of 35.4%. In silico docking studies predicted similar binding pattern of compound 19 on androgen receptor as hydroxyflutamide. Compound 19 appears to be a unique scaffold with promising activities against androgen associated prostatic disorders in males like prostate cancer and BPH and associated depression. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.03.036

文献信息

• Novel aryl piperazines for alleviation of ‘andropause’ associated prostatic disorders and depression
  作者：Sonal Gupta、Deepti Pandey、Dhanaraju Mandalapu、Vikas Sharma、Mahendra Shukla、Seema Singh、Nidhi Singh、Santosh Kumar Yadav、Dilip Kumar Tanpula、Surabhi Singh、Jagdamba P. Maikhuri、Shubha Shukla、Jawahar Lal、Mohammad I. Siddiqi、Gopal Gupta、Vishnu L. Sharma

  DOI：10.1016/j.ejmech.2017.03.036

  日期：2017.5

  A series of seventeen piperazine derivatives have been synthesized and biologically evaluated for the management of andropause-associated prostatic disorders and depression. Five compounds 16,19, 20, 21 and 22 significantly inhibited proliferation of androgen-sensitive LNCaP prostatic cell line with EC50 values of 12.4 mu M, 15.6 11.8 mu M, 10.4 mu M, 12.2 mu M respectively and decreased Ca2+ entry through adrenergic-receptor alpha(1A) blocking activity. Anti-androgenic behaviour of compound 19 and 22 was evident by decreased luciferase activity. The high EC50 value in AR-negative cells PC3 and DU145 suggested that the cytotoxicity of compounds was due to AR down regulation. Compound 19 reduced the prostate weight of rats by 53.8%. Further, forced-swimming and tail-suspension tests revealed antidepressant-like activity of compound 19, lacking effects on neuromuscular co-ordination. In silico ADMET predictions revealed that the compound 19 had good oral absorption, aqueous solubility, non-hepatotoxic and good affinity for plasma protein binding. Pharmacokinetic and tissue uptake of 19 at 10 mg/kg demonstrated an oral bioavailability of 35.4%. In silico docking studies predicted similar binding pattern of compound 19 on androgen receptor as hydroxyflutamide. Compound 19 appears to be a unique scaffold with promising activities against androgen associated prostatic disorders in males like prostate cancer and BPH and associated depression. (C) 2017 Elsevier Masson SAS. All rights reserved.