二(4-氟苯基)(苯基)乙腈 | 289656-82-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 中文名称: 二(4-氟苯基)(苯基)乙腈
• 中文别名: 2,2-双(4-氟苯基)-2-苯基乙腈
• 英文名称: bis(4-fluorophenyl)phenylacetonitrile
• 英文别名: 2,2-Bis(4-fluorophenyl)-2-phenylacetonitrile
• CAS: 289656-82-2
• 化学式: C₂₀H₁₃F₂N
• mdl: MFCD09743760
• 分子量: 305.327
• InChiKey: OIIGTIPIURUMQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  23.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  二(4-氟苯基)(苯基)乙腈 以28的产率得到塞尼卡泊
  参考文献：
  名称：

  Gardos channel antagonists

  摘要：

  本发明揭示了一种新型的钾离子通量抑制剂。这些抑制剂在生物介质中具有惊人的抗降解性和相对于非氟代同系物的增强体内半衰期。这些化合物的使用方法包括治疗镰状细胞贫血、预防红细胞脱水和抑制钾离子通量。

  公开号：

  US06288122B1
• 作为产物：
  描述：

  4,4'-二氟二苯甲酮 在 indium(III) chloride 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 3.0h， 生成 二(4-氟苯基)(苯基)乙腈
  参考文献：
  名称：

  Process Development and Optimization for Production of a Potassium Ion Channel Blocker, ICA-17043

  摘要：

  A scalable process for the manufacture of a potassium ion channel blocker was developed and optimized. Key features of the process include an optimized Grignard reaction, a direct cyanation of the intermediate trityl alcohol derivative, and an improved nitrile hydrolysis protocol, relative to the original acidic hydrolysis conditions, to generate the crude active pharmaceutical ingredient (API) with >95% HPLC purity. The Grignard and the cyanation reactions could be telescoped, resulting in an improved throughput compared to the original four-step process. An effective recrystallization of the API was also developed and the process scaled up to manufacture multiple batches at the pilot scale.

  DOI：

  10.1021/op3000916

文献信息

• 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。
• WO2007/75849
  申请人：——

  公开号：——

  公开（公告）日：——
• Novel Inhibitors of the Gardos Channel for the Treatment of Sickle Cell Disease
  作者：Grant A. McNaughton-Smith、J. Ford Burns、Jonathan W. Stocker、Gregory C. Rigdon、Christopher Creech、Susan Arrington、Tara Shelton、Lucia de Franceschi

  DOI：10.1021/jm070663s

  日期：2008.2.1

  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.
• Drugs Fut. 2003, 28, 854-858
  作者：

  DOI：——

  日期：——