[4-[4-[4-(Trifluoromethoxy)phenyl]piperazin-1-yl]phenyl]methanamine | 1426520-98-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: [4-[4-[4-(Trifluoromethoxy)phenyl]piperazin-1-yl]phenyl]methanamine
• CAS: 1426520-98-0
• 化学式: C₁₈H₂₀F₃N₃O
• 分子量: 351.372
• InChiKey: PCFGNTFXQSJCOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  41.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  7-chloro-2-ethylimidazo[1,2-a]pyridine-3-carboxylic acid 、 [4-[4-[4-(Trifluoromethoxy)phenyl]piperazin-1-yl]phenyl]methanamine 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 7-chloro-2-ethyl-N-(4-(4-(4-(trifluoromethoxy)phenyl)piperazin-1-yl)benzyl)imidazo[1,2-a]pyridine-3-carboxamide
  参考文献：
  名称：

  Lead Optimization of a Novel Series of Imidazo[1,2-a]pyridine Amides Leading to a Clinical Candidate (Q203) as a Multi- and Extensively-Drug-Resistant Anti-tuberculosis Agent

  摘要：

  A critical unmet clinical need to combat the global tuberculosis epidemic is the development of potent agents capable of reducing the time of multi-drug-resistant (MDR) and extensively-drug-resistant (XDR) tuberculosis therapy. In this paper, we report on the optimization of imidazo[1,2-a]pyridine amide (IPA) lead compound 1, which led to the design and synthesis of Q203 (50). We found that the amide linker with IPA core is very important for activity against Mycobacterium tuberculosis H37Rv. Linearity and lipophilicity of the amine part in the IPA series play a critical role in improving in vitro and in vivo efficacy and pharmacokinetic profile. The optimized IPAs 49 and 50 showed not only excellent oral bioavailability (80.2% and 90.7%, respectively) with high exposure of the area under curve (AUC) but also displayed significant colony-forming unit (CFU) reduction (1.52 and 3.13 log10 reduction at 10 mg/kg dosing level, respectively) in mouse lung.

  DOI：

  10.1021/jm5003606
• 作为产物：
  描述：

  对溴三氟甲氧基苯 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 lithium aluminium tetrahydride 、 potassium carbonate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二甲基亚砜 为溶剂， 反应 38.0h， 生成 [4-[4-[4-(Trifluoromethoxy)phenyl]piperazin-1-yl]phenyl]methanamine
  参考文献：
  名称：

  [EN] ANTI-INFECTIVE COMPOUNDS
  [FR] COMPOSÉS ANTI-INFECTIEUX

  摘要：

  公开号：

  WO2015014993A3

文献信息

• Pyrrolidine‐containing or Piperazine‐containing Nitrofuranylamides: Design, Synthesis, and <i>In Vitro</i> Anti‐mycobacterial Activities
  作者：Shi‐Jia Zhao、Zao‐Sheng Lv、Jia‐Lun Deng、Guang‐De Zhang、Zhi Xu

  DOI：10.1002/jhet.3340

  日期：2018.12

  the design, synthesis, and in vitro anti‐mycobacterial activities of 11 pyrrolidine‐containing or piperazine‐containing nitrofuranylamides. Results revealed that all derivatives 3a–k endowed with excellent activity [minimum inhibitory concentration (MIC): <0.016–0.482 μg/mL] against Mycobacterium tuberculosis (MTB) H37Rv strain and more than half of them were more potent than the first‐line anti‐tuberculosis

  我们在此报告11种含吡咯烷或含哌嗪的硝基呋喃酰胺的设计，合成和体外抗分枝杆菌活性。结果表明，所有衍生物3a-k均具有抗结核分枝杆菌（MTB）H37Rv菌株的优异活性[最小抑菌浓度（MIC）：<0.016-0.482μg/ mL] ，其中一半以上比一线药物更有效抗结核药异烟肼（MIC：0.078μg/ mL）和利福平（MIC：0.078μg/ mL）。针对两种临床分离的对异烟肼和利福平均具有抗药性的多重耐药MTB菌株，进一步评估了活性最高的六种衍生物。特别是其中的三个3a，3c，3d和3j（MIC：1.412–3.230μg/ mL）对两种临床分离的耐多药MTB菌株显示出令人鼓舞的活性，可以作为进一步研究的起点。
• Antibacterial compounds
  申请人：Janssen Sciences Ireland UC

  公开号：US10364232B2

  公开（公告）日：2019-07-30

  The present invention relates to the following compounds wherein the integers are as defined in the description, and where the compounds may be useful as medicaments, for instance for use in the treatment of tuberculosis.

  本发明涉及以下化合物 其中的整数如描述中所定义，这些化合物可用作药物，例如用于治疗结核病。
• ANTI-INFECTIVE COMPOUNDS
  申请人：Institut Pasteur Korea

  公开号：EP3027615B1

  公开（公告）日：2021-07-21
• Anti-Infective Compounds
  申请人：INSTITUT PASTEUR KOREA

  公开号：US20160185774A1

  公开（公告）日：2016-06-30

  The present invention relates to small molecule compounds and their use in the treatment of bacterial infections, in particular Tuberculosis.
• Antibacterial Compounds
  申请人：Janssen Sciences Ireland UC

  公开号：US20180186768A1

  公开（公告）日：2018-07-05

  The present invention relates to the following compounds wherein the integers are as defined in the description, and where the compounds may be useful as medicaments, for instance for use in the treatment of tuberculosis.