5-(4-chlorophenyl)-N-(3-methylphenyl)furan-2-carboxamide | 213910-94-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(4-chlorophenyl)-N-(3-methylphenyl)furan-2-carboxamide
• CAS: 213910-94-2
• 化学式: C₁₈H₁₄ClNO₂
• 分子量: 311.768
• InChiKey: DJDFKPIUUFKRNI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(4-chlorophenyl)-N-(3-methylphenyl)furan-2-carboxamide 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以99%的产率得到5-(4-chlorophenyl)-N-(3-methylphenyl)furan-2-carbothioamide
  参考文献：
  名称：

  Discovery and Biological Evaluation of 5-Aryl-2-furfuramides, Potent and Selective Blockers of the Na_v1.8 Sodium Channel with Efficacy in Models of Neuropathic and Inflammatory Pain

  摘要：

  Na(v)1.8 (also known as PN3) is a tetrodotoxin-resistant (TTx-r) voltage-gated sodium channel (VGSC) that is highly expressed on small diameter sensory neurons and has been implicated in the pathophysiology of inflammatory and neuropathic pain. Recent studies using an Na(v)1.8 antisense oligonucleotide in an animal model of chronic pain indicated that selective blockade of Na(v)1.8 was analgesic and could provide effective analgesia with a reduction in the adverse events associated with nonselective VGSC blocking therapeutic agents. Herein, we describe the preparation and characterization of a series of 5-substituted 2-furfuramides, which are potent, voltage-dependent blockers (IC50 < 10 nM) of the human Na(v)1.8 channel. Selected derivatives, such as 7 and 27, also blocked TTx-r sodium currents in rat dorsal root ganglia (DRG) neurons with comparable potency and displayed > 100-fold selectivity versus human sodium (Na(v)1.2, Na(v)1.5, Na(v)1.7) and human ether-a-go-go (hERG) channels. Following systemic administration, compounds 7 and dose-dependently reduced neuropathic and inflammatory pain in experimental rodent models.

  DOI：

  10.1021/jm070637u
• 作为产物：
  描述：

  5-溴-N-(3-甲基苯基)-2-糠酰胺 、 4-氯苯硼酸 在 bis-triphenylphosphine-palladium(II) chloride sodium carbonate 作用下， 以 水 、 异丙醇 为溶剂， 反应 5.0h， 以79%的产率得到5-(4-chlorophenyl)-N-(3-methylphenyl)furan-2-carboxamide
  参考文献：
  名称：

  Discovery and Biological Evaluation of 5-Aryl-2-furfuramides, Potent and Selective Blockers of the Na_v1.8 Sodium Channel with Efficacy in Models of Neuropathic and Inflammatory Pain

  摘要：

  Na(v)1.8 (also known as PN3) is a tetrodotoxin-resistant (TTx-r) voltage-gated sodium channel (VGSC) that is highly expressed on small diameter sensory neurons and has been implicated in the pathophysiology of inflammatory and neuropathic pain. Recent studies using an Na(v)1.8 antisense oligonucleotide in an animal model of chronic pain indicated that selective blockade of Na(v)1.8 was analgesic and could provide effective analgesia with a reduction in the adverse events associated with nonselective VGSC blocking therapeutic agents. Herein, we describe the preparation and characterization of a series of 5-substituted 2-furfuramides, which are potent, voltage-dependent blockers (IC50 < 10 nM) of the human Na(v)1.8 channel. Selected derivatives, such as 7 and 27, also blocked TTx-r sodium currents in rat dorsal root ganglia (DRG) neurons with comparable potency and displayed > 100-fold selectivity versus human sodium (Na(v)1.2, Na(v)1.5, Na(v)1.7) and human ether-a-go-go (hERG) channels. Following systemic administration, compounds 7 and dose-dependently reduced neuropathic and inflammatory pain in experimental rodent models.

  DOI：

  10.1021/jm070637u

文献信息

• Discovery and Biological Evaluation of 5-Aryl-2-furfuramides, Potent and Selective Blockers of the Na_v1.8 Sodium Channel with Efficacy in Models of Neuropathic and Inflammatory Pain
  作者：Michael E. Kort、Irene Drizin、Robert J. Gregg、Marc J. C. Scanio、Lei Shi、Michael F. Gross、Robert N. Atkinson、Matthew S. Johnson、Gregory J. Pacofsky、James B. Thomas、William A. Carroll、Michael J. Krambis、Dong Liu、Char-Chang Shieh、XuFeng Zhang、Gricelda Hernandez、Joseph P. Mikusa、Chengmin Zhong、Shailen Joshi、Prisca Honore、Rosemarie Roeloffs、Kennan C. Marsh、Bernard P. Murray、Jinrong Liu、Stephen Werness、Connie R. Faltynek、Douglas S. Krafte、Michael F. Jarvis、Mark L. Chapman、Brian E. Marron

  DOI：10.1021/jm070637u

  日期：2008.2.1

  Na(v)1.8 (also known as PN3) is a tetrodotoxin-resistant (TTx-r) voltage-gated sodium channel (VGSC) that is highly expressed on small diameter sensory neurons and has been implicated in the pathophysiology of inflammatory and neuropathic pain. Recent studies using an Na(v)1.8 antisense oligonucleotide in an animal model of chronic pain indicated that selective blockade of Na(v)1.8 was analgesic and could provide effective analgesia with a reduction in the adverse events associated with nonselective VGSC blocking therapeutic agents. Herein, we describe the preparation and characterization of a series of 5-substituted 2-furfuramides, which are potent, voltage-dependent blockers (IC50 < 10 nM) of the human Na(v)1.8 channel. Selected derivatives, such as 7 and 27, also blocked TTx-r sodium currents in rat dorsal root ganglia (DRG) neurons with comparable potency and displayed > 100-fold selectivity versus human sodium (Na(v)1.2, Na(v)1.5, Na(v)1.7) and human ether-a-go-go (hERG) channels. Following systemic administration, compounds 7 and dose-dependently reduced neuropathic and inflammatory pain in experimental rodent models.