benzyl-(2-chloro-3-nitro-6-trifluoromethylpyridin-4-yl)amine | 947144-18-5

• 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: benzyl-(2-chloro-3-nitro-6-trifluoromethylpyridin-4-yl)amine
• 英文别名: benzyl-(2-chloro-3-nitro-6-trifluoromethyl-pyridine-4-yl)-amine；Benzyl-(2-chloro-3-nitro-6-trifluoromethyl-pyridin-4-yl)-amine；N-benzyl-2-chloro-3-nitro-6-(trifluoromethyl)pyridin-4-amine
• CAS: 947144-18-5
• 化学式: C₁₃H₉ClF₃N₃O₂
• 分子量: 331.682
• InChiKey: CRMMMUSYLFXFKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  70.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  benzyl-(2-chloro-3-nitro-6-trifluoromethylpyridin-4-yl)amine 在 硫酸 、 Me-THF 、 氨 、 potassium carbonate 、 三乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 生成
  参考文献：
  名称：

  Design and optimisation of orally active TLR7 agonists for the treatment of hepatitis C virus infection

  摘要：

  The synthesis and structure-activity relationships of a series of novel interferon inducers are described. Pharmacokinetic studies and efficacy assessment of a series of 8-oxo-3-deazapurine analogues led to the identification of compound 33, a potent and selective agonist of the TLR7 receptor with an excellent in vivo efficacy profile in a mouse model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.092
• 作为产物：
  描述：

  4-(苄基氨基)-3-硝基-6-(三氟甲基)吡啶-2-醇 在 苯膦酰二氯 作用下， 以 二氯甲烷 为溶剂， 反应 22.0h， 以77%的产率得到benzyl-(2-chloro-3-nitro-6-trifluoromethylpyridin-4-yl)amine
  参考文献：
  名称：

  实用的Toll样受体激动剂PF-4171455的合成：4-氨基-1-苄基-6-三氟甲基-1,3-二氢咪唑并[4,5 - c ]吡啶-2-酮

  摘要：

  描述了用于制造Toll样受体（TLR7）激动剂PF-4171455（1）的可扩展方法的开发和实施。用于以毫克量合成1的初始路线不适合大规模合成以提供块状材料。如药物化学和研究-API之间的转移的一部分，用于协作的千规模合成提供了一种用于路由目的的拟合1。合成的关键方面包括（i）在四个步骤中安全，实用地合成关键的硝基吡啶酮中间体7，（ii）顺序进行区域选择性氯化以选择性官能化7（iii）使用氨基甲酸酯作为束缚的羰基，可实现1的有效区域特异性合成。

  DOI：

  10.1021/op200021a

文献信息

• NOVEL PHARMACEUTICALS
  申请人：Jones Peter

  公开号：US20070197478A1

  公开（公告）日：2007-08-23

  The present invention relates to immune response modifiers of formula (I), which act selectively through agonism, of Toll-Like Receptors (TLRs), uses thereof, processes for the preparation thereof, intermediates used in the preparation thereof and compositions containing said inhibitors. These inhibitors have utility in a variety of therapeutic areas including the treatment of infectious disease such as Hepatitis (e.g. HCV, HBV), genetically related viral infection and cancer.

  本发明涉及公式（I）的免疫应答调节剂，通过对Toll样受体（TLRs）的激动作用具有选择性，其用途，其制备方法，用于其制备的中间体以及含有所述抑制剂的组合物。这些抑制剂在包括治疗传染病（如肝炎（例如HCV，HBV），遗传相关病毒感染和癌症在内的各种治疗领域中具有用途。
• Spray dried formulation
  申请人：Ketner Rodney James

  公开号：US20100029667A1

  公开（公告）日：2010-02-04

  Pharmaceutical compositions comprising a poorly water soluble ionizable drug, a cationic species and a dispersion polymer are disclosed, together with a process for forming the compositions. The neutral form of the drug has (i) a solubility of less than 1 mg/ml, in aqueous solution at a pH between 6 and 7, (ii) a solubility of less than 20 mg/mL in a volatile organic solvent, and (iii) an acidic pKa value of greater than 5. At least 90 wt % of the drug in the solid dispersion being in a non-crystalline form. The drug, the cationic species, and the dispersion polymer constitute at least 80 wt % of the solid dispersion.

  本发明涉及一种包含难溶性离子型药物、阳离子物种和分散聚合物的制药组合物，以及制备该组合物的方法。该药物的中性形式在pH为6到7的水溶液中的溶解度小于1 mg/mL，在挥发性有机溶剂中的溶解度小于20 mg/mL，并且具有大于5的酸性pKa值。在固体分散物中至少90重量％的药物处于非晶态形式。该药物、阳离子物种和分散聚合物构成固体分散物的至少80重量％。
• Pharmaceuticals
  申请人：Pfizer Inc.

  公开号：US07691877B2

  公开（公告）日：2010-04-06

  The present invention relates to immune response modifiers of formula (I), which act selectively through agonism, of Toll-Like Receptors (TLRs), uses thereof, processes for the preparation thereof, intermediates used in the preparation thereof and compositions containing said inhibitors. These inhibitors have utility in a variety of therapeutic areas including the treatment of infectious disease such as Hepatitis (e.g. HCV, HBV), genetically related viral infection and cancer.

  本发明涉及公式（I）的免疫应答调节剂，其通过Toll样受体（TLRs）的激动作用选择性地发挥作用，其应用，制备过程，制备中使用的中间体以及含有所述抑制剂的组合物。这些抑制剂在多种治疗领域中具有实用性，包括治疗传染性疾病，如肝炎（例如HCV，HBV），遗传相关的病毒感染和癌症。
• Discovery of a highly potent series of TLR7 agonists
  作者：Peter Jones、David C. Pryde、Thien-Duc Tran、Fiona M. Adam、Gerwyn Bish、Frederick Calo、Guiseppe Ciaramella、Rachel Dixon、Jonathan Duckworth、David N.A. Fox、Duncan A. Hay、James Hitchin、Nigel Horscroft、Martin Howard、Carl Laxton、Tanya Parkinson、Gemma Parsons、Katie Proctor、Mya C. Smith、Nicholas Smith、Amy Thomas

  DOI：10.1016/j.bmcl.2011.07.076

  日期：2011.10

  The discovery of a series of highly potent and novel TLR7 agonist interferon inducers is described. Structure- activity relationships are presented, along with pharmacokinetic studies of a lead molecule from this series of N9-pyridylmethyl-8-oxo-3-deazapurine analogues. A rationale for the very high potency observed is offered. An investigation of the clearance mechanism of this class of compounds in rat was carried out, resulting in aldehyde oxidase mediated oxidation being identified as a key component of the high clearance observed. A possible solution to this problem is discussed. (C) 2011 Elsevier Ltd. All rights reserved.
• WO2008/47201
  申请人：——

  公开号：——

  公开（公告）日：——