2,2,2-tris(4-fluoro-phenyl)-acetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 2,2,2-tris(4-fluoro-phenyl)-acetamide
• 英文别名: 2,2,2-Tris(4-fluorophenyl)acetamide
• 化学式: C₂₀H₁₄F₃NO
• 分子量: 341.332
• InChiKey: NEYVEJOLUVXNDA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  43.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,2,2-tris(4-fluorophenyl)acetonitrile 在 硫酸 、 溶剂黄146 作用下， 反应 3.0h， 以168 mg的产率得到2,2,2-tris(4-fluoro-phenyl)-acetamide
  参考文献：
  名称：

  Novel Inhibitors of the Gardos Channel for the Treatment of Sickle Cell Disease

  摘要：

  Sickle cell disease (SCD) is a hereditary condition characterized by deformation of red blood cells (RBCs). This phenomenon is due to the presence of abnormal hemoglobin that polymerizes upon deoxygenation. This effect is exacerbated when dehydrated RBCs experience a loss of both water and potassium salts. One critical pathway for the regulation of potassium efflux from RBCs is the Gardos channel, a calcium-activated potassium channel. This paper describes the synthesis and biological evaluation of a series of potent inhibitors of the Gardos channel. The goal was to identify compounds that were potent and selective inhibitors of the channel but had improved pharmacokinetic properties compared to 1, Clotrimazole. Several triarylamides such as 10 and 21 were potent inhibitors of the Gardos channel (IC50 of < 10 nM) and active in a mouse model of SCD. Compound 21 (ICA-17043) was advanced into phase 3 clinical trials for SCD.

  DOI：

  10.1021/jm070663s

文献信息

• Imines as ion channel modulators
  申请人：Wang Xiaodong

  公开号：US20060178346A1

  公开（公告）日：2006-08-10

  The present invention provides a class of chemical compounds useful in the treatment of sickle cell disease, diseases characterized by unwanted or abnormal cell proliferation and for the treatment of ocular disorders such as glaucoma. The active compounds are tri-(aryl or heteroaryl) methane compounds or analogues thereof which further comprise an imine moiety and where the tertiary carbon atom can be replaced with a different atom such as Si, Ge, N or P. The compounds enhance resistance to degradation in a biological medium, inhibit potassium flux in a cell, reduce mammalian cell proliferation, reduce the Gardos channel of erythrocytes, reduce sickle erythrocyte dehydration and/or delay the occurrence of erythrocyte sickling or deformation.

  本发明提供了一类化合物，可用于治疗镰状细胞病、以异常或不良细胞增殖为特征的疾病，以及治疗眼部疾病，如青光眼。这些活性化合物是三(芳基或杂环芳基)甲烷化合物或其类似物，进一步包括亚胺基团，其中三级碳原子可被硅、锗、氮或磷等不同原子取代。这些化合物增强了在生物介质中的抗降解性，抑制细胞内的钾离子通量，减少哺乳动物细胞的增殖，减少红细胞的Gardos通道，减少镰状红细胞的脱水，并/或延迟红细胞的镰刀化或变形的发生。
• TREATMENT METHODS USING TRIARYL METHANE COMPOUNDS
  申请人：Castle Neil A.

  公开号：US20090036538A1

  公开（公告）日：2009-02-05

  The use of novel inhibitors of potassium flux is disclosed for the treatment of inflammatory processes, such as multiple sclerosis, insulin-dependent (type I) diabetes mellitus, rheumatoid arthritis, peripheral neuritis and pulmonary hypertension. The compounds are also of use in treating and preventing stroke. These inhibitors have a high specificity for the IK1 channel and greater stability relative to non-fluorine substituted homologues.

  本发明公开了使用新型钾离子通道抑制剂治疗炎症过程的方法，例如多发性硬化症、胰岛素依赖型（I型）糖尿病、类风湿性关节炎、周围神经炎和肺动脉高压。这些化合物还可用于治疗和预防中风。这些抑制剂对IK1通道具有高度的特异性，并且相对于非氟代同系物具有更高的稳定性。
• Treatment methods using triaryl methane compounds
  申请人：Castle A. Neil

  公开号：US20070185209A1

  公开（公告）日：2007-08-09

  The use of novel inhibitors of potassium flux is disclosed for the treatment of inflammatory processes, such as multiple sclerosis, insulin-dependent (type I) diabetes mellitus, rheumatoid arthritis, peripheral neuritis and pulmonary hypertension. The compounds are also of use in treating and preventing stroke. These inhibitors have a high specificity for the IK1 channel and greater stability relative to non-fluorine substituted homologues.

  本发明揭示了使用新型钾通量抑制剂治疗炎症过程，例如多发性硬化症、胰岛素依赖性（I型）糖尿病、类风湿性关节炎、周围神经炎和肺动脉高压。这些化合物还可用于治疗和预防中风。这些抑制剂对IK1通道具有高度特异性，相对于非氟取代同源物具有更高的稳定性。
• Methods for treating malaria using potassium channel inhibitors
  申请人：THE CHILDREN'S MEDICAL CENTER CORPORATION

  公开号：US10179115B2

  公开（公告）日：2019-01-15

  The present invention relates to the field of anti-malarials. In particular, the disclosure relates to methods for treating malaria in a subject by administering to said subject a potassium channel inhibitor. The disclosed potassium channel inhibitors provide wide bioavailability, long half-life, and good toxicity profiles while showing high potency for killing parasites which cause malaria. In certain exemplary embodiments, the potassium channel inhibitor is an inhibitor of calcium-activated potassium channels. In certain exemplary embodiments, the potassium channel inhibitor is an inhibitor of the Gardos channel.

  本发明涉及抗疟疾领域。特别是，本发明涉及通过向受试者施用钾离子通道抑制剂来治疗疟疾的方法。本发明公开的钾离子通道抑制剂具有生物利用度高、半衰期长、毒性低的特点，同时在杀死引起疟疾的寄生虫方面表现出很高的效力。在某些示例性实施方案中，钾通道抑制剂是钙激活钾通道的抑制剂。在某些示例性实施方案中，钾通道抑制剂是加多斯通道抑制剂。
• GARDOS CHANNEL ANTAGONISTS
  申请人：Icagen, Inc.

  公开号：EP1158971B1

  公开（公告）日：2007-08-22