6-[4-(三氟甲氧基)苯基]吡嗪-2-甲酸 | 1258269-13-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 6-[4-(三氟甲氧基)苯基]吡嗪-2-甲酸
• 英文名称: 6-(4-trifluoromethoxyphenyl)-pyrazine-2-carboxylic acid
• 英文别名: 6-[4-(Trifluoromethoxy)phenyl]pyrazine-2-carboxylic Acid；6-[4-(trifluoromethoxy)phenyl]pyrazine-2-carboxylic acid
• CAS: 1258269-13-4
• 化学式: C₁₂H₇F₃N₂O₃
• 分子量: 284.194
• InChiKey: OSXYZXXMTIHCMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  72.3
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-[4-(三氟甲氧基)苯基]吡嗪-2-甲酸 在 草酰氯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以99%的产率得到6-(4-trifluoromethoxyphenyl)-pyrazine-2-carbonyl chloride
  参考文献：
  名称：

  Discovery and biological evaluation of potent, selective, orally bioavailable, pyrazine-based blockers of the Nav1.8 sodium channel with efficacy in a model of neuropathic 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. It has been implicated in the pathophysiology of inflammatory and neuropathic pain, and we envisioned that selective blockade of Na(v)1.8 would be analgesic, while reducing adverse events typically associated with non-selective VGSC blocking therapeutic agents. Herein, we describe the preparation and characterization of a series of 6-aryl-2-pyrazinecarboxamides, which are potent blockers of the human Na(v)1.8 channel and also block TTx-r sodium currents in rat dorsal root ganglia (DRG) neurons. Selected derivatives display selectivity versus human Na(v)1.2. We further demonstrate that an example from this series is orally bioavailable and produces antinociceptive activity in vivo in a rodent model of neuropathic pain following oral administration. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.09.057
• 作为产物：
  描述：

  methyl-6-(4-trifluoromethoxyphenyl)-2-pyrazinecarboxylate 在 sodium hydroxide 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 以99%的产率得到6-[4-(三氟甲氧基)苯基]吡嗪-2-甲酸
  参考文献：
  名称：

  Discovery and biological evaluation of potent, selective, orally bioavailable, pyrazine-based blockers of the Nav1.8 sodium channel with efficacy in a model of neuropathic 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. It has been implicated in the pathophysiology of inflammatory and neuropathic pain, and we envisioned that selective blockade of Na(v)1.8 would be analgesic, while reducing adverse events typically associated with non-selective VGSC blocking therapeutic agents. Herein, we describe the preparation and characterization of a series of 6-aryl-2-pyrazinecarboxamides, which are potent blockers of the human Na(v)1.8 channel and also block TTx-r sodium currents in rat dorsal root ganglia (DRG) neurons. Selected derivatives display selectivity versus human Na(v)1.2. We further demonstrate that an example from this series is orally bioavailable and produces antinociceptive activity in vivo in a rodent model of neuropathic pain following oral administration. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.09.057

文献信息

• Subtype-selective Nav1.8 sodium channel blockers: Identification of potent, orally active nicotinamide derivatives
  作者：Michael E. Kort、Robert N. Atkinson、James B. Thomas、Irene Drizin、Matthew S. Johnson、Matthew A. Secrest、Robert J. Gregg、Marc J.C. Scanio、Lei Shi、Ahmed H. Hakeem、Mark A. Matulenko、Mark L. Chapman、Michael J. Krambis、Dong Liu、Char-Chang Shieh、XuFeng Zhang、Gricelda Simler、Joseph P. Mikusa、Chengmin Zhong、Shailen Joshi、Prisca Honore、Rosemarie Roeloffs、Stephen Werness、Brett Antonio、Kennan C. Marsh、Connie R. Faltynek、Douglas S. Krafte、Michael F. Jarvis、Brian E. Marron

  DOI：10.1016/j.bmcl.2010.08.121

  日期：2010.11

  A series of aryl-substituted nicotinamide derivatives with selective inhibitory activity against the Na(v)1.8 sodium channel is reported. Replacement of the furan nucleus and homologation of the anilide linker in subtype-selective blocker A-803467 (1) provided potent, selective derivatives with improved aqueous solubility and oral bioavailability. Representative compounds from this series displayed efficacy in rat models of inflammatory and neuropathic pain. (C) 2010 Elsevier Ltd. All rights reserved.
• Discovery and biological evaluation of potent, selective, orally bioavailable, pyrazine-based blockers of the Nav1.8 sodium channel with efficacy in a model of neuropathic pain
  作者：Marc J.C. Scanio、Lei Shi、Irene Drizin、Robert J. Gregg、Robert N. Atkinson、James B. Thomas、Matthew S. Johnson、Mark L. Chapman、Dong Liu、Michael J. Krambis

  DOI：10.1016/j.bmc.2010.09.057

  日期：2010.11.15

  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. It has been implicated in the pathophysiology of inflammatory and neuropathic pain, and we envisioned that selective blockade of Na(v)1.8 would be analgesic, while reducing adverse events typically associated with non-selective VGSC blocking therapeutic agents. Herein, we describe the preparation and characterization of a series of 6-aryl-2-pyrazinecarboxamides, which are potent blockers of the human Na(v)1.8 channel and also block TTx-r sodium currents in rat dorsal root ganglia (DRG) neurons. Selected derivatives display selectivity versus human Na(v)1.2. We further demonstrate that an example from this series is orally bioavailable and produces antinociceptive activity in vivo in a rodent model of neuropathic pain following oral administration. (C) 2010 Elsevier Ltd. All rights reserved.