Methyl 1-[(2,6-dichlorophenyl)methyl]triazole-4-carboxylate

• 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: Methyl 1-[(2,6-dichlorophenyl)methyl]triazole-4-carboxylate
• 化学式: C₁₁H₉Cl₂N₃O₂
• 分子量: 286.11
• InChiKey: ZRBLDNOBNVDUDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  57
• 氢给体数：
  0
• 氢受体数：
  4

文献信息

• [EN] PHARMACOLOGICAL MODULATORS OF NAV1.1 VOLTAGE-GATED SODIUM CHANNELS ASSOCIATED WITH MECHANICAL PAIN<br/>[FR] MODULATEURS PHARMACOLOGIQUES DES CANAUX SODIQUES VOLTAGE-DÉPENDANTS NAV1.1 ASSOCIÉS À DES DOULEURS MÉCANIQUES
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2017147379A1

  公开（公告）日：2017-08-31

  The present invention provides the use of compounds which selectively block the Nav1.1 subtype of voltage-gated sodium (Nav) channels, whose role in nociception and pain has been unexplored. The present invention demonstrates that Nav1.1-expressing fibers are modality specific nociceptors: their activation elicits robust pain behaviors without neurogenic inflammation and produces profound hypersensitivity to mechanical, but not thermal, stimuli. In the gut, high-threshold mechanosensitive fibers also express Nav1.1 and show enhanced toxin sensitivity in a model of irritable bowel syndrome. The present invention provides an unexpected role for Nav1.1 in regulating the excitability of sensory nerve fibers that underlie mechanical pain, and provides methods of screening for other peptides and small molecules that can modulate Nav1.1 channels and their use in treatment of neurological disorders.

  本发明提供了选择性阻断电压门控钠（Nav）通道的Nav1.1亚型的化合物的使用，其在疼痛感知和疼痛中的作用尚未被探索。本发明证明Nav1.1表达的纤维是特定于模态的伤害感受器：它们的激活引起强烈的疼痛行为，没有神经源性炎症，并产生对机械刺激的深度过敏，而不是对热刺激的过敏。在肠道中，高阈值机械敏感纤维也表达Nav1.1，并在肠易激综合征模型中显示出增强的毒素敏感性。本发明提供了Nav1.1在调节感觉神经纤维的兴奋性方面的意外作用，这些感觉神经纤维是机械性疼痛的基础，并提供了筛选其他肽和小分子以调节Nav1.1通道及其在治疗神经系统疾病中的使用的方法。
• RUFINAMIDE AND DERIVATIVES AND THEIR USE IN MODULATING THE GATING PROCESS OF HUMAN VOLTAGE-GATED SODIUM CHANNELS
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US20150336904A1

  公开（公告）日：2015-11-26

  The present invention provides compounds of formula I which are capable of inhibition of the activation of hNav1.1 or hNav1.6 sodium channels in neurons. Pharmaceutical compositions comprising these compounds are also provided. Methods for prevention and treatment of neurological disorders, including, for example, seizures and seizure disorders, including Lennox-Gastaut Syndrome, Dravet syndrome, epileptic encephalopathies, autism, Familial hemiplegic migraine (FHM), anxiety disorders, including Post-traumatic stress disorder (PTSD), panic disorder and obsessive-compulsive disorder, neuropathic pain, and Rett syndrome by administration of these compounds are also provided.
• DERIVATIVES OF RUFINAMIDE AND THEIR USE IN INHIBTION OF THE ACTIVATION OF HUMAN VOLTAGE-GATED SODIUM CHANNELS
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US20170029382A1

  公开（公告）日：2017-02-02

  The present invention provides compounds of formula I which are capable of inhibition of the activation of hNav1.1 or hNav1.6 sodium channels in neurons. Pharmaceutical compositions comprising these compounds are also provided. Methods for prevention and treatment of neurological disorders, including, for example, seizures and seizure disorders, including Lennox-Gastaut Syndrome, Dravet syndrome, epileptic encephalopathies, autism, Familial hemiplegic migraine (FHM), anxiety disorders, including Post-traumatic stress disorder (PTSD), panic disorder and obsessive-compulsive disorder, neuropathic pain, and Rett syndrome by administration of these compounds are also provided.
• US9505727B2
  申请人：——

  公开号：US9505727B2

  公开（公告）日：2016-11-29
• US9771335B2
  申请人：——

  公开号：US9771335B2

  公开（公告）日：2017-09-26