N-cyclopropyl-1-phenethyl-4-(N-phenylpropionamido)piperidine-4-carboxamide

• 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: N-cyclopropyl-1-phenethyl-4-(N-phenylpropionamido)piperidine-4-carboxamide
• 英文别名: N-cyclopropyl-1-(2-phenylethyl)-4-(N-propanoylanilino)piperidine-4-carboxamide
• 化学式: C₂₆H₃₃N₃O₂
• 分子量: 419.567
• InChiKey: MUPMANMOMAWXBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  52.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-(2-苯乙基)-4-哌啶酮 、 环丙基异腈 、 丙酸 、 苯胺 以 甲醇 为溶剂， 反应 18.0h， 生成 N-cyclopropyl-1-phenethyl-4-(N-phenylpropionamido)piperidine-4-carboxamide
  参考文献：
  名称：

  Synthesis of Carfentanil Amide Opioids Using the Ugi Multicomponent Reaction

  摘要：

  We report a novel approach to synthesize carfentanil amide analogues utilizing the isocyanide-based four-component Ugi multicomponent reaction. A small library of bis-amide analogues of carfentanil was created using N-alkylpiperidones, aniline, propionic acid, and various aliphatic isocyanides. Our lead compound showed high affinity for mu (MOR) and delta opioid receptors (DOR) with no appreciable affinity for kappa (KOR) receptors in radioligand binding assays. The compound was found to be a mixed MOR agonist/partial DOR agonist in [S-35]GTP gamma S functional assays, and it showed moderate analgesic potency in vivo. The compound showed no visible signs of physical dependence or constipation in mice. In addition, it produced less respiratory depression than morphine. Most mixed MOR/DOR opioids reported in the literature are peptides and thereby systemically inactive. Our approach utilizing a multicomponent reaction has the promise to deliver potent and efficacious small-molecule analgesics with potential clinical utility.

  DOI：

  10.1021/acschemneuro.5b00137

文献信息

• Synthesis of Carfentanil Amide Opioids Using the Ugi Multicomponent Reaction
  作者：András Váradi、Travis C. Palmer、Nathan Haselton、Daniel Afonin、Joan J. Subrath、Valerie Le Rouzic、Amanda Hunkele、Gavril W. Pasternak、Gina F. Marrone、Attila Borics、Susruta Majumdar

  DOI：10.1021/acschemneuro.5b00137

  日期：2015.9.16

  We report a novel approach to synthesize carfentanil amide analogues utilizing the isocyanide-based four-component Ugi multicomponent reaction. A small library of bis-amide analogues of carfentanil was created using N-alkylpiperidones, aniline, propionic acid, and various aliphatic isocyanides. Our lead compound showed high affinity for mu (MOR) and delta opioid receptors (DOR) with no appreciable affinity for kappa (KOR) receptors in radioligand binding assays. The compound was found to be a mixed MOR agonist/partial DOR agonist in [S-35]GTP gamma S functional assays, and it showed moderate analgesic potency in vivo. The compound showed no visible signs of physical dependence or constipation in mice. In addition, it produced less respiratory depression than morphine. Most mixed MOR/DOR opioids reported in the literature are peptides and thereby systemically inactive. Our approach utilizing a multicomponent reaction has the promise to deliver potent and efficacious small-molecule analgesics with potential clinical utility.