1-benzyl-4-(3-methoxyphenylamino)piperidine-4-carbonitrile | 974-71-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-benzyl-4-(3-methoxyphenylamino)piperidine-4-carbonitrile
• 英文别名: 1-Benzyl-4-cyano-4-m-methoxyanilinopiperidin；1-Benzyl-4-cyan-4-(3-methoxyanilino)-piperidin；1-Benzyl-4-(3-methoxyanilino)piperidine-4-carbonitrile
• CAS: 974-71-0
• 化学式: C₂₀H₂₃N₃O
• mdl: MFCD22054085
• 分子量: 321.422
• InChiKey: UURJJSSYMOZFMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  48.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-benzyl-4-(3-methoxyphenylamino)piperidine-4-carbonitrile 在 氨 、 氢气 作用下， 以 甲醇 为溶剂， 以95%的产率得到4-(aminomethyl)-1-benzyl-N-(3-methoxyphenyl)piperidin-4-amine
  参考文献：
  名称：

  Nonpeptide Small Molecule Agonist and Antagonist Original Leads for Neuropeptide FF1 and FF2 Receptors

  摘要：

  Neuropeptide FF1 and FF2 receptors (NPFF1-R and NPFF2-R), and their endogenous ligand NPFF, are one of only several systems responsible for mediating opioid-induced hyperalgesia, tolerance, and dependence. Currently, no small molecules displaying good affinity or selectivity for either subtype have been reported, to decipher the role of NPFF2-R as it relates to opioid-mediated analgesia, for further exploration of NPFF1-R, or for medication development for either subtype. We report the first nonpeptide small molecule scaffold for NPFF1,2-R, the guanidino-piperidines, and SAR studies resulting in the discovery of a NPFF1 agonist (7b, K-i = 487 +/- 117 nM), a NPFF1 antagonist (46, K-i = 81 +/- 17 nM), and a NPFF2 partial antagonist (53a, K-i = 30 +/- 5 nM), which serve as leads for the development of pharmacological probes and potential therapeutic agents. Testing of 46 alone was without effect in the mouse 48 degrees C warm-water tail-withdrawal test, but pretreatment with 46 prevented NPFF-induced hyperalgesia.

  DOI：

  10.1021/jm500989n
• 作为产物：
  描述：

  N-甲基-4-哌啶酮 在 lithium aluminium tetrahydride 、 溶剂黄146 作用下， 以 乙醚 、 水 为溶剂， 反应 8.0h， 生成 1-benzyl-4-(3-methoxyphenylamino)piperidine-4-carbonitrile
  参考文献：
  名称：

  Nonpeptide Small Molecule Agonist and Antagonist Original Leads for Neuropeptide FF1 and FF2 Receptors

  摘要：

  Neuropeptide FF1 and FF2 receptors (NPFF1-R and NPFF2-R), and their endogenous ligand NPFF, are one of only several systems responsible for mediating opioid-induced hyperalgesia, tolerance, and dependence. Currently, no small molecules displaying good affinity or selectivity for either subtype have been reported, to decipher the role of NPFF2-R as it relates to opioid-mediated analgesia, for further exploration of NPFF1-R, or for medication development for either subtype. We report the first nonpeptide small molecule scaffold for NPFF1,2-R, the guanidino-piperidines, and SAR studies resulting in the discovery of a NPFF1 agonist (7b, K-i = 487 +/- 117 nM), a NPFF1 antagonist (46, K-i = 81 +/- 17 nM), and a NPFF2 partial antagonist (53a, K-i = 30 +/- 5 nM), which serve as leads for the development of pharmacological probes and potential therapeutic agents. Testing of 46 alone was without effect in the mouse 48 degrees C warm-water tail-withdrawal test, but pretreatment with 46 prevented NPFF-induced hyperalgesia.

  DOI：

  10.1021/jm500989n

文献信息

• DAELE P. G. H. VAN; DE BRUYN M. F. L.; BOEY J. M.; SANCZUK S.; AGTEN J. T+, ARZNEIMITTEL-FORSCH. <ARZN-AD>, 1976, 26, NO 8, 1521-1531
  作者：DAELE P. G. H. VAN、 DE BRUYN M. F. L.、 BOEY J. M.、 SANCZUK S.、 AGTEN J. T+

  DOI：——

  日期：——
• Nonpeptide Small Molecule Agonist and Antagonist Original Leads for Neuropeptide FF1 and FF2 Receptors
  作者：V. Blair Journigan、Christophe Mésangeau、Neha Vyas、Shainnel O. Eans、Stephen J. Cutler、Jay P. McLaughlin、Catherine Mollereau、Christopher R. McCurdy

  DOI：10.1021/jm500989n

  日期：2014.11.13

  Neuropeptide FF1 and FF2 receptors (NPFF1-R and NPFF2-R), and their endogenous ligand NPFF, are one of only several systems responsible for mediating opioid-induced hyperalgesia, tolerance, and dependence. Currently, no small molecules displaying good affinity or selectivity for either subtype have been reported, to decipher the role of NPFF2-R as it relates to opioid-mediated analgesia, for further exploration of NPFF1-R, or for medication development for either subtype. We report the first nonpeptide small molecule scaffold for NPFF1,2-R, the guanidino-piperidines, and SAR studies resulting in the discovery of a NPFF1 agonist (7b, K-i = 487 +/- 117 nM), a NPFF1 antagonist (46, K-i = 81 +/- 17 nM), and a NPFF2 partial antagonist (53a, K-i = 30 +/- 5 nM), which serve as leads for the development of pharmacological probes and potential therapeutic agents. Testing of 46 alone was without effect in the mouse 48 degrees C warm-water tail-withdrawal test, but pretreatment with 46 prevented NPFF-induced hyperalgesia.