1,2-bis(4-(pyridin-2-yl)piperazin-1-yl)propane | 102443-71-0

• 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-bis(4-(pyridin-2-yl)piperazin-1-yl)propane
• 英文别名: 1,3-bis-(4-[2]pyridyl-piperazino)-propane；1,3-Bis-(4-[2]pyridyl-piperazino)-propan；1-Pyridin-2-yl-4-[3-(4-pyridin-2-ylpiperazin-1-yl)propyl]piperazine
• CAS: 102443-71-0
• 化学式: C₂₁H₃₀N₆
• 分子量: 366.509
• InChiKey: RMDLUAQAQGBIOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(2-吡啶基)哌嗪 、 1-溴-3-氯丙烷 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 5.25h， 以66%的产率得到1,2-bis(4-(pyridin-2-yl)piperazin-1-yl)propane
  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

• Substituted alkylenedipiperazines
  申请人：AMERICAN CYANAMID CO

  公开号：US02837522A1

  公开（公告）日：1958-06-03
• 2-{4-[3-(4-Aryl/heteroaryl-1-piperazinyl)propoxy]phenyl}-2H-benzotriazoles and their N-oxides as ligands for serotonin and dopamine receptors
  作者：Anna Sparatore、Mara Goegan、Alfredo Cagnotto、Fabio Sparatore

  DOI：10.1016/s0014-827x(99)00046-4

  日期：1999.6

  A small set of 2-4-[3-(4-aryl/heteroaryl-piperazinyl)propoxy]phenyl}-2H-benzotriazoles and corresponding N-oxides were prepared. The synthesized compounds were able to bind on some serotonin (5-HT1A, 5-HT2A) and dopamine (D-2, D-3) receptors, while displaying poor or no affinity for 5-HT1B, 5-NT2C, 5-HT3, and 5-HT4 subtypes. The strong contribution of the N-oxide function for the binding on 5-HT1A, D-2 and D-3 receptors is noteworthy. For 2-4-[3-[4-(2-methoxyphenyl)-1-piperazinyl]propoxy]phenyl}-2H-benzotriazol-1-oxide (4b), the binding constants (K-i) were 11.9 (5-HT1A) and 10.5 nM (D-3). In a general pharmacological screening, the 2-4-[3-(4-phenyl-1-piperazinyl)propoxy]phenyl}-2H-benzotriazole (3a) exhibited only very weak activities, with the exception of protecting mice from cyanide-induced hypoxia. (C) 1999 Elsevier Science S.A. All rights reserved.