N-{1-[2-(2,4-difluorophenyl)-2-fluoroethyl]piperidin-4-yl}-N-phenylpropanamide

• 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-{1-[2-(2,4-difluorophenyl)-2-fluoroethyl]piperidin-4-yl}-N-phenylpropanamide
• 英文别名: N-[1-[2-(2,4-difluorophenyl)-2-fluoroethyl]piperidin-4-yl]-N-phenylpropanamide
• 化学式: C₂₂H₂₅F₃N₂O
• 分子量: 390.449
• InChiKey: FJXRHQMYUOVNNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-{1-[2-(2,4-difluorophenyl)-2-hydroxyethyl]piperidin-4-yl}-N-phenylpropanamide 在 二乙胺基三氟化硫 、 triethylamine tris(hydrogen fluoride) 作用下， 以 二氯甲烷 为溶剂， 以28%的产率得到N-{1-[2-(2,4-difluorophenyl)-2-fluoroethyl]piperidin-4-yl}-N-phenylpropanamide
  参考文献：
  名称：

  [EN] FLUORINATED COMPOUNDS AS PH-SENSITIVE ANALGESICS
  [FR] COMPOSÉS FLUORÉS UTILES EN TANT QU'ANALGÉSIQUES SENSIBLES AU PH

  摘要：

  本发明提供了芬太尼的新型氟化物类似物及其使用方法。具体而言，芬太尼的这些类似物可用于治疗疼痛，包括与炎症相关的疼痛或慢性疼痛。

  公开号：

  WO2020006563A1

文献信息

• [EN] FLUORINATED COMPOUNDS AS PH-SENSITIVE ANALGESICS<br/>[FR] COMPOSÉS FLUORÉS UTILES EN TANT QU'ANALGÉSIQUES SENSIBLES AU PH
  申请人：UNIV MARQUETTE

  公开号：WO2020006563A1

  公开（公告）日：2020-01-02

  The present invention provides novel fluorinated analogs of fentanyl and methods of use. Specifically, the analogs of fentanyl can be used for the treatment of pain, including inflammation associated pain or chronic pain.

  本发明提供了芬太尼的新型氟化物类似物及其使用方法。具体而言，芬太尼的这些类似物可用于治疗疼痛，包括与炎症相关的疼痛或慢性疼痛。
• β-Fluorofentanyls Are pH-Sensitive Mu Opioid Receptor Agonists
  作者：Ricardo Rosas、Xi-Ping Huang、Bryan L. Roth、Chris Dockendorff

  DOI：10.1021/acsmedchemlett.9b00335

  日期：2019.9.12

  The concept recently postulated by Stein and co-workers (Science 2017, 355, 966) that mu opioid receptor (MOR) agonists possessing amines with attenuated basicity show pH-dependent activity and can selectively act at damaged, low pH tissues has been additionally supported by in vitro studies reported here. We synthesized and tested analogs of fentanyl possessing one or two fluorine atoms at the beta position of the phenethylamine side chain, with additional fluorines optionally added to the benzene ring of the side chain. These compounds were synthesized in 1 to 3 steps from commercial building blocks. The novel bis-fluorinated analog RR-49 showed superior pH sensitivity, with full efficacy relative to DAMGO, but with 19-fold higher potency (IC50) in a MOR cAMP assay at pH 6.5 versus 7.4. Such compounds hold significant promise as analgesics for inflammatory pain with reduced abuse potential.