2,2-bis-(2-fluoro-phenyl)-2-(4-fluoro-phenyl)-ethanamide

• 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-bis-(2-fluoro-phenyl)-2-(4-fluoro-phenyl)-ethanamide
• 英文别名: 2,2-bis-(2-fluoro-phenyl)-2-(4-fluoro-phenyl)-acetamide；2,2-Bis(2-fluorophenyl)-2-(4-fluorophenyl)acetamide
• 化学式: C₂₀H₁₄F₃NO
• 分子量: 341.332
• InChiKey: OHDYQIXWGRLRPZ-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-Bis(2-fluorophenyl)-2-(4-fluorophenyl)acetonitrile 在 硫酸 、 溶剂黄146 作用下， 反应 3.0h， 以147 mg的产率得到2,2-bis-(2-fluoro-phenyl)-2-(4-fluoro-phenyl)-ethanamide
  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

• 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。
• COMPOSITIONS AND METHODS FOR MODULATING CELL-CELL FUSION VIA INTERMEDIATE-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNELS
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2358750A2

  公开（公告）日：2011-08-24
• METHODS FOR TREATING MALARIA USING POTASSIUM CHANNEL INHIBITORS
  申请人：THE CHILDREN'S MEDICAL CENTER CORPORATION

  公开号：US20180042872A1

  公开（公告）日：2018-02-15

  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.
• US9428568B2
  申请人：——

  公开号：US9428568B2

  公开（公告）日：2016-08-30