1-(1,3-benzodioxol-5-ylmethyl)-4-(4-bromobenzyl)piperazine | 355396-68-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 1-(1,3-benzodioxol-5-ylmethyl)-4-(4-bromobenzyl)piperazine
• 英文别名: 1-(1,3-benzodioxol-5-ylmethyl)-4-[(4-bromophenyl)methyl]piperazine
• CAS: 355396-68-8
• 化学式: C₁₉H₂₁BrN₂O₂
• 分子量: 389.292
• InChiKey: CWMPQMJUWBXPIW-UHFFFAOYSA-N

物化性质

• 沸点：
  475.5±40.0 °C(Predicted)
• 密度：
  1.428±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  24.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  对溴溴苄 、 1-胡椒基哌嗪 以 二氯甲烷 为溶剂， 反应 24.0h， 以63%的产率得到1-(1,3-benzodioxol-5-ylmethyl)-4-(4-bromobenzyl)piperazine
  参考文献：
  名称：

  Synthesis and biological evaluation of novel 4-benzylpiperazine ligands for sigma-1 receptor imaging

  摘要：

  We report the synthesis and evaluation of 4-benzylpiperazine ligands (BP-CH3, BP-F, BP-Br, BP-I, and BP-NO2) as potential sigma(1) receptor ligands. The X-ray crystal structure of BP-Br, which crystallized with monoclinic space group P2(1)/c, has been determined. In vitro competition binding assays showed that all the five ligands exhibit low nanomolar affinity for sigma(1) receptors (K-i = 0.43-0.91 nM) and high subtype selectivity (sigma(2) receptor: K-i = 40-61 nM; K-i sigma(2)/K-i sigma(1) = 52-94). [I-125] BP-I (1-(1,3-benzodioxol-5-ylmethyl)-4-(4-iodobenzyl) piperazine) was prepared in 53 +/- 10% isolated radiochemical yield, with radiochemical purity of > 99% by HPLC analysis after purification, via iododestannylation of the corresponding tributyltin precursor. The log D value of [I-125] BP-I was found to be 2.98 +/- 0.17, which is within the range expected to give high brain uptake. Biodistribution studies in mice demonstrated relatively high concentration of radiolabeled substances in organs known to contain sigma(1) receptors, including the brain, lung, kidney, heart, and spleen. Administration of haloperidol 5 min prior to injection of [I-125] BP-I significantly reduced the concentration of radioactivity in the above-mentioned organs. The accumulation of radiolabeled substance in the thyroid was quite low suggesting that [I-125] BP-I is relatively stable to in vivo deiodination. These findings suggest that the binding of [I-125] BP-I to sigma(1) receptors in vivo is specific. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.03.037

文献信息

• [EN] METHODS OF USING PIPERAZINE COMPOUNDS IN TREATING SODIUM CHANNEL-MEDIATED DISEASES OR CONDITIONS<br/>[FR] PROCÉDÉS D'UTILISATON DE COMPOSÉS PIPÉRAZINE DANS LE TRAITEMENT DE MALADIES OU ÉTATS MÉDIÉS PAR LE CANAL SODIUM
  申请人：XENON PHARMACEUTICALS INC

  公开号：WO2008147864A2

  公开（公告）日：2008-12-04

  [EN] This invention is directed to piperazine compounds, as stereoisomers, enantiomers, tautomers thereof or mixtures thereof; or pharmaceutically acceptable salts, solvates or prodrugs thereof, for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain.
  [FR] L'invention concerne des composés pipérazine, tels que des stéréoisomères, des énantiomères, des tautomères et des mélanges de ces derniers, ou des sels, solvates ou promédicaments pharmaceutiquement acceptables de ces derniers, qui sont destinés au traitement et/ou à la prévention de maladies ou états médiés par le canal sodium, comme la douleur.