[5-(4-tert-Butylphenyl)furan-2-yl]-(4-cyclohexylpiperazin-1-yl)-methanone | 1043543-51-6

• 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-tert-Butylphenyl)furan-2-yl]-(4-cyclohexylpiperazin-1-yl)-methanone
• 英文别名: [5-(4-tert-butylphenyl)furan-2-yl]-(4-cyclohexylpiperazin-1-yl)methanone
• CAS: 1043543-51-6
• 化学式: C₂₅H₃₄N₂O₂
• 分子量: 394.557
• InChiKey: HJTNQQWICWEECK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 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：

  (5-bromofuran-2-yl)-(4-cyclohexylpiperazin-1-yl)-methanone 、 4-叔丁基苯硼酸 在 bis-triphenylphosphine-palladium(II) chloride sodium carbonate 作用下， 以 水 、 甲苯 为溶剂， 反应 16.0h， 以55%的产率得到[5-(4-tert-Butylphenyl)furan-2-yl]-(4-cyclohexylpiperazin-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

• SYSTEMS AND METHODS OF SELECTING COMPOUNDS WITH REDUCED RISK OF CARDIOTOXICITY USING CARDIAC SODIUM ION CHANNEL MODELS
  申请人：THE GOVERNORS OF THE UNIVERSITY OF ALBERTA

  公开号：US20180068053A1

  公开（公告）日：2018-03-08

  Provided herein are systems and methods for selecting compounds that have reduced risk of cardiotoxicity or which are not likely to be cardiotoxic. As an example, a system and method can include a computational dynamic model combined with a high throughput screening in silico that mimics an important ion channels associated with cardiotoxicity, namely the human cardiac sodium ion (hNa v 1.5) channel). In certain embodiments, steered molecular dynamics simulations are used to identify key residues of the channel's permeation pathways that are then used in the high throughput screening. Also provided herein are systems and methods for redesigning compounds that are predicted to be cardiotoxic based on the model and the high throughput screening.
• 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。