2-(2-fluorophenyl)-2,2-diphenylacetonitrile | 197526-04-8

• 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-fluorophenyl)-2,2-diphenylacetonitrile
• 英文别名: (2-fluorophenyl)-diphenylacetonitrile
• CAS: 197526-04-8
• 化学式: C₂₀H₁₄FN
• 分子量: 287.336
• InChiKey: OVESKCFYTJXKMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  22
• 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：
  2

反应信息

• 作为反应物：
  描述：

  2-(2-fluorophenyl)-2,2-diphenylacetonitrile 在 硫酸 、 溶剂黄146 作用下， 反应 3.0h， 以411 mg的产率得到2-(2-Fluorophenyl)-2,2-diphenylacetamide
  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
• 作为产物：
  描述：

  1-[氯(二苯基)甲基]-2-氟苯 以 甲苯 为溶剂， 生成 2-(2-fluorophenyl)-2,2-diphenylacetonitrile
  参考文献：
  名称：

  Use of triaryl methane compounds for inhibiting unwanted cellular proliferation associated with inflammatory disease

  摘要：

  本发明提供了一类化合物，可用作治疗镰状细胞病和以不需要或异常细胞增殖为特征的疾病的有效药物，特别是与不需要的细胞增殖相关的炎症性疾病。这些活性化合物是取代的三芳基甲烷化合物或其类似物，其中芳基之一或多个被取代为杂芳基、环烷基或杂环烷基，以及/或者第三级碳原子被其他原子如硅、锗、氮或磷所取代，这些化合物抑制哺乳动物细胞增殖，抑制红细胞的Gardos通道，减少镰状红细胞的脱水，和/或延迟红细胞的镰刀形成或变形的发生。

  公开号：

  US06331564B1

文献信息

• Triaryl methane compounds and analogues thereof useful for the treatment
  申请人：Children's Medical Center Corporation

  公开号：US06028103A1

  公开（公告）日：2000-02-22

  The present invention provides a class of chemical compounds useful as efficacious drugs in the treatment of sickle cell disease and diseases characterized by unwanted or abnormal cell proliferation. The active compounds are substituted triaryl methane compounds or analogues thereof where one or more of the aryl groups is replaced with a heteroaryl, cycloalkyl or heterocycloalkyl group and/or the tertiary carbon atom is replaced with a different atom such as Si, Ge, N or P. The compounds inhibit mammalian cell proliferation, inhibit 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，可作为治疗镰状细胞病和以不需要或异常细胞增殖为特征的疾病的有效药物。这些活性化合物是取代的三芳基甲烷化合物或其类似物，其中芳基中的一个或多个被取代为杂芳基、环烷基或杂环烷基，或者第三级碳原子被硅、锗、氮或磷等不同的原子取代。这些化合物抑制哺乳动物细胞的增殖，抑制红细胞的Gardos通道，减少镰状红细胞的脱水，延迟红细胞的镰刀变形或变形的发生。
• 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。
• Compounds, Methods And Devices for Inhibiting Neoproliferative Changes in Blood Vessel Walls
  申请人：Koehler Ralf

  公开号：US20090048270A1

  公开（公告）日：2009-02-19

  Methods, compositions and devices for inhibiting neoproliferative changes in blood vessel walls or other anatomical structures. One or more compounds of Formula I or I-A set forth herein are administered systemically and/or locally to human or veterinary patients to deter or prevent unwanted proliferative changes in blood vessels or other anatomical structures. The invention may be used to deter or prevent stenosis or restenosis of arteries following angioplasty and/or stent placement. In one embodiment, there is provided an implantable stent or stent graft from which one or more compounds of the present invention will elute or otherwise be delivered into an affected blood vessel wall.

  本发明提供了抑制血管壁或其他解剖结构中新生增生的方法、组合物和装置。本发明中的公式I或I-A中的一个或多个化合物被系统性和/或局部地用于人类或兽医患者，以防止或预防血管或其他解剖结构中不必要的增生变化。本发明可用于防止或预防血管成形术和/或支架置入后的动脉狭窄或再狭窄。在一种实施方式中，提供了一种可植入的支架或支架移植物，其中本发明的一个或多个化合物将被释放或以其他方式输送到受影响的血管壁中。
• Non-peptide inhibition of T-lymphocyte activation and therapies related thereto
  申请人：Chandy George K.

  公开号：US20070293554A1

  公开（公告）日：2007-12-20

  Compounds, preparations and methods for immunosuppressive treatment of autoimmune disorders, graft rejection and/or graft/host disease. Therapeutically effective amounts of certain substituted triarylmethane compounds, such as 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole, are administered to mammalian patients to selectively inhibit the calcium-activated K + channel (IKCa1) in lymphocytes, monocytes, macrophages, platelets or endothelial cells without concomitant inhibition of P450-dependent enzyme systems, resulting in reduction of antigen-, cytokine-, or mitogen-induced calcium entry through store operated calcium channels in these cells, suppression of cytokine production by these cells, and inhibition of activation of these cells. Such inhibition of the Ca ++ activated K + channel (IKCa1) prevents the pre-Ca ++ stage of cell activation and thus causes immunosuppression and an anti-inflammatory response.

  化合物、制剂和方法用于免疫抑制治疗自身免疫性疾病、移植排斥和/或移植宿主病。将某些取代三芳基甲烷化合物，例如1-[(2-氯苯基)二苯甲基]-1H-吡唑酮，以治疗剂量给哺乳动物患者，以选择性抑制淋巴细胞、单核细胞、巨噬细胞、血小板或内皮细胞中的钙激活K+通道（IKCa1），而不伴随P450依赖性酶系统的抑制，从而减少这些细胞中抗原、细胞因子或诱导剂引起的钙离子进入，抑制这些细胞的细胞因子产生，并抑制这些细胞的激活。这种对Ca++激活的K+通道（IKCa1）的抑制防止了细胞激活的前Ca++阶段，从而引起免疫抑制和抗炎反应。
• 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。