[5-(4-Chlorophenyl)furan-2-yl]-[4-(dimethylamino)piperidin-1-yl]methanone | 1007197-93-4

• 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: [5-(4-Chlorophenyl)furan-2-yl]-[4-(dimethylamino)piperidin-1-yl]methanone
• CAS: 1007197-93-4
• 化学式: C₁₈H₂₁ClN₂O₂
• 分子量: 332.83
• InChiKey: CEKBOFCQHHPDJK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  36.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-二甲氨基哌啶 、 5-(4-chloro-phenyl)-furan-2-carbonyl chloride 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以0.140 g的产率得到[5-(4-Chlorophenyl)furan-2-yl]-[4-(dimethylamino)piperidin-1-yl]methanone
  参考文献：
  名称：

  发现了有效的呋喃哌嗪钠通道阻滞剂，用于治疗神经性疼痛。

  摘要：

  报道了一种新型的呋喃基电压门控钠通道阻滞剂的合成和药理学表征。评价了化合物阻断抗河豚毒素的钠通道Na（v）1.8（PN3）以及Na（v）1.2和Na（v）1.5亚型的能力。与临床使用的钠通道阻滞剂美西律和拉莫三嗪相比，该系列的基准化合物在神经性疼痛的啮齿动物模型中具有增强的效力，口服生物利用度和强大的功效，并具有改善的中枢神经系统和心血管安全性。

  DOI：

  10.1016/j.bmc.2008.05.003

文献信息

• Discovery of potent furan piperazine sodium channel blockers for treatment of neuropathic pain
  作者：Irene Drizin、Robert J. Gregg、Marc J.C. Scanio、Lei Shi、Michael F. Gross、Robert N. Atkinson、James B. Thomas、Matthew S. Johnson、William A. Carroll、Brian E. Marron、Mark L. Chapman、Dong Liu、Michael J. Krambis、Char-Chang Shieh、XuFeng Zhang、Gricelda Hernandez、Donna M. Gauvin、Joseph P. Mikusa、Chang Z. Zhu、Shailen Joshi、Prisca Honore、Kennan C. Marsh、Rosemarie Roeloffs、Stephen Werness、Douglas S. Krafte、Michael F. Jarvis、Connie R. Faltynek、Michael E. Kort

  DOI：10.1016/j.bmc.2008.05.003

  日期：2008.6

  The synthesis and pharmacological characterization of a novel furan-based class of voltage-gated sodium channel blockers is reported. Compounds were evaluated for their ability to block the tetrodotoxin-resistant sodium channel Na(v)1.8 (PN3) as well as the Na(v)1.2 and Na(v)1.5 subtypes. Benchmark compounds from this series possessed enhanced potency, oral bioavailability, and robust efficacy in a

  报道了一种新型的呋喃基电压门控钠通道阻滞剂的合成和药理学表征。评价了化合物阻断抗河豚毒素的钠通道Na（v）1.8（PN3）以及Na（v）1.2和Na（v）1.5亚型的能力。与临床使用的钠通道阻滞剂美西律和拉莫三嗪相比，该系列的基准化合物在神经性疼痛的啮齿动物模型中具有增强的效力，口服生物利用度和强大的功效，并具有改善的中枢神经系统和心血管安全性。
• 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.