4-苯基-1-(3-苯基-丙基)-哌啶-4-甲腈 | 1041870-85-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 4-苯基-1-(3-苯基-丙基)-哌啶-4-甲腈
• 英文名称: 1-Phenylpropyl-4-phenylpiperidine-4-carbonitrile
• 英文别名: 4-phenyl-1-(3-phenylpropyl)piperidine-4-carbonitrile
• CAS: 1041870-85-2
• 化学式: C₂₁H₂₄N₂
• 分子量: 304.435
• InChiKey: XYOLVZKHEFSPGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-苯基-1-(3-苯基-丙基)-哌啶-4-甲腈 、 乙醇 在 硫酸 作用下， 生成 4-phenyl-1-(3-phenyl-propyl)-piperidine-4-carboxylic acid ethyl ester
  参考文献：
  名称：

  阿片类药物和外排转运蛋白。第 1 部分：哌替啶 N-取代类似物的 P-糖蛋白底物活性。

  摘要：

  P-糖蛋白 (P-gp) 是一种外排转运蛋白，在吗啡和羟考酮耐受大鼠的血脑屏障中上调。大量研究表明，许多临床使用的阿片类镇痛药是 P-gp 的底物，表明 P-gp 的上调可能有助于阿片类药物中枢耐受的发展。本文的研究重点是哌替啶系列化合物中 P-gp 底物活性的 SAR 开发，并表明效力更强的哌替啶类似物 N-苯基丁基-N-去甲哌替啶作为 P-gp 底物的活性较低，并且有潜力用作研究 P-gp 对阿片类药物中枢耐受性发展的贡献的工具。

  DOI：

  10.1016/j.bmcl.2006.12.042
• 作为产物：
  描述：

  4-苯基哌啶-4-甲腈 、 1-溴-3-苯基丙烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-苯基-1-(3-苯基-丙基)-哌啶-4-甲腈
  参考文献：
  名称：

  Nitrile analogs of meperidine as high affinity and selective sigma-1 receptor ligands

  摘要：

  A series of N-substituted-4-cyano-4-phenylpiperidine analogs were synthesized and evaluated for binding affinity at opioid receptors and showed no affinity. The series similarity to previously reported sigma ligands prompted analysis at a receptors to determine the SAR for affinity at sigma receptors. Within the N-substituent series the saturated analogs showed increased affinity at both a receptors. Optimal chain length in the N-arylalkyl series for sigma(1) and sigma(2) receptors proved to be N-propylphenyl; extension to a four carbon chain dramatically decreased affinity at both receptors. Substituents in the 4-position affect only sigma(1) affinity; no change in affinity at sigma(2) was shown. The N-isobutyl, N-phenylpropyl, and N-benzyl analogs are worth pursuing due to their good affinity and selectivity at the sigma(1) receptor, whereas the N-benzyl analog exhibits the greatest selectivity for sigma(1). (c) 2007 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2007.09.026

文献信息

• Opioids and efflux transporters. Part 1: P-Glycoprotein substrate activity of N-substituted analogs of meperidine
  作者：Susan L. Mercer、Hazem E. Hassan、Christopher W. Cunningham、Natalie D. Eddington、Andrew Coop

  DOI：10.1016/j.bmcl.2006.12.042

  日期：2007.3

  to the development of central tolerance to opioids. The studies herein focus on the development of SAR for P-gp substrate activity in the meperidine series of compounds, and show that a meperidine analog of greater potency, N-phenylbutyl-N-normeperidine, has low activity as a P-gp substrate and has the potential to be utilized as a tool to study the contribution of P-gp to the development of central

  P-糖蛋白 (P-gp) 是一种外排转运蛋白，在吗啡和羟考酮耐受大鼠的血脑屏障中上调。大量研究表明，许多临床使用的阿片类镇痛药是 P-gp 的底物，表明 P-gp 的上调可能有助于阿片类药物中枢耐受的发展。本文的研究重点是哌替啶系列化合物中 P-gp 底物活性的 SAR 开发，并表明效力更强的哌替啶类似物 N-苯基丁基-N-去甲哌替啶作为 P-gp 底物的活性较低，并且有潜力用作研究 P-gp 对阿片类药物中枢耐受性发展的贡献的工具。
• Nitrile analogs of meperidine as high affinity and selective sigma-1 receptor ligands
  作者：Susan L. Mercer、Jamaluddin Shaikh、John R. Traynor、Rae R. Matsumoto、Andrew Coop

  DOI：10.1016/j.ejmech.2007.09.026

  日期：2008.6

  A series of N-substituted-4-cyano-4-phenylpiperidine analogs were synthesized and evaluated for binding affinity at opioid receptors and showed no affinity. The series similarity to previously reported sigma ligands prompted analysis at a receptors to determine the SAR for affinity at sigma receptors. Within the N-substituent series the saturated analogs showed increased affinity at both a receptors. Optimal chain length in the N-arylalkyl series for sigma(1) and sigma(2) receptors proved to be N-propylphenyl; extension to a four carbon chain dramatically decreased affinity at both receptors. Substituents in the 4-position affect only sigma(1) affinity; no change in affinity at sigma(2) was shown. The N-isobutyl, N-phenylpropyl, and N-benzyl analogs are worth pursuing due to their good affinity and selectivity at the sigma(1) receptor, whereas the N-benzyl analog exhibits the greatest selectivity for sigma(1). (c) 2007 Elsevier Masson SAS. All rights reserved.