4-((1,4-dioxaspiro[4.5]decan-8-ylmethyl)amino)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide

• 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: 4-((1,4-dioxaspiro[4.5]decan-8-ylmethyl)amino)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide
• 英文别名: 5-chloro-4-(1,4-dioxaspiro[4.5]decan-8-ylmethylamino)-2-fluoro-N-(1,3-thiazol-2-yl)benzenesulfonamide
• 化学式: C₁₈H₂₁ClFN₃O₄S₂
• 分子量: 461.966
• InChiKey: AHSYZDMXZZIITC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  5-氯-2,4-二氟苯磺酰氯 在 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 4-((1,4-dioxaspiro[4.5]decan-8-ylmethyl)amino)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide
  参考文献：
  名称：

  Discovery of non-zwitterionic aryl sulfonamides as Nav1.7 inhibitors with efficacy in preclinical behavioral models and translational measures of nociceptive neuron activation

  摘要：

  Since zwitterionic benzenesulfonamide Na(v)1.7 inhibitors suffer from poor membrane permeability, we sought to eliminate this characteristic by replacing the basic moiety with non-basic bicyclic acetals and monocyclic ethers. These efforts led to the discovery of the non-zwitterionic aryl sulfonamide 49 as a selective Na(v)1.7 inhibitor with improved membrane permeability. Despite its moderate cellular activity, 49 exhibited robust efficacy in mouse models of neuropathic and inflammatory pain and modulated translational electromyogram measures associated with activation of nociceptive neurons. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.08.012

文献信息

• Discovery of non-zwitterionic aryl sulfonamides as Nav1.7 inhibitors with efficacy in preclinical behavioral models and translational measures of nociceptive neuron activation
  作者：Yong-Jin Wu、Jason Guernon、Andrea McClure、Guanglin Luo、Ramkumar Rajamani、Alicia Ng、Amy Easton、Amy Newton、Clotilde Bourin、Dawn Parker、Kathleen Mosure、Omar Barnaby、Matthew G. Soars、Ronald J. Knox、Michele Matchett、Rick Pieschl、James Herrington、Ping Chen、D.V. Sivarao、Linda J. Bristow、Nicholas A. Meanwell、Joanne Bronson、Richard Olson、Lorin A. Thompson、Carolyn Dzierba

  DOI：10.1016/j.bmc.2017.08.012

  日期：2017.10

  Since zwitterionic benzenesulfonamide Na(v)1.7 inhibitors suffer from poor membrane permeability, we sought to eliminate this characteristic by replacing the basic moiety with non-basic bicyclic acetals and monocyclic ethers. These efforts led to the discovery of the non-zwitterionic aryl sulfonamide 49 as a selective Na(v)1.7 inhibitor with improved membrane permeability. Despite its moderate cellular activity, 49 exhibited robust efficacy in mouse models of neuropathic and inflammatory pain and modulated translational electromyogram measures associated with activation of nociceptive neurons. (C) 2017 Elsevier Ltd. All rights reserved.