4-(2-bromoacetyl)-N-(3,3,3-trifluoropropyl)benzamide | 1589819-00-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(2-bromoacetyl)-N-(3,3,3-trifluoropropyl)benzamide
• CAS: 1589819-00-0
• 化学式: C₁₂H₁₁BrF₃NO₂
• 分子量: 338.124
• InChiKey: NZNBEYCZDVDCDS-UHFFFAOYSA-N

物化性质

• 沸点：
  414.7±45.0 °C(predicted)
• 密度：
  1.510±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(2-bromoacetyl)-N-(3,3,3-trifluoropropyl)benzamide 在 三甲基氯硅烷 作用下， 以 水 为溶剂， 生成 Isopropyl-2-(4-(4-(3,3,3-trifluoropropylcarbamoyl)phenyl)thiazol-2-yl)-acetat
  参考文献：
  名称：

  Fragment-Based Optimized EthR Inhibitors with in Vivo Ethionamide Boosting Activity

  摘要：

  Killing more than one million people each year, tuberculosis remains the leading cause of death from a single infectious agent. The growing threat of multidrug-resistant strains of Mycobacterium tuberculosis stresses the need for alternative therapies. EthR, a mycobacterial transcriptional regulator, is involved in the control of the bioactivation of the second-line drug ethionamide. We have previously reported the discovery of in vitro nanomolar boosters of ethionamide through fragment-based approaches. In this study, we have further explored the structure-activity and structure-property relationships in this chemical family. By combining structure-based drug design and in vitro evaluation of the compounds, we identified a new oxadiazole compound as the first fragment-based ethionamide booster which proved to be active in vivo, in an acute model of tuberculosis infection.

  DOI：

  10.1021/acsinfecdis.9b00277
• 作为产物：
  描述：

  4-乙酰基苯甲酸 在 盐酸 、 1-羟基苯并三唑 作用下， 以 甲醇 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(2-bromoacetyl)-N-(3,3,3-trifluoropropyl)benzamide
  参考文献：
  名称：

  COMPOUNDS FOR USE IN THE TREATMENT OF MYCOBACTERIAL INFECTIONS

  摘要：

  本发明涉及通式（I）的化合物： 其中Y和Z从CH和N中选择；T从CO或SO2中选择；n为1到3；R1代表选择的一种基团，例如从C1-C3烷基链中未取代或取代的氟，未取代或取代的环状，氰基，偶氮基，烷氧基和苯基；R从偶氮基，氰基，炔烃基和2-苯并噻唑基以及一个可选择取代的具有五个顶点的芳香杂环中选择；以及其在治疗细菌和分枝杆菌感染，如肺结核、麻风和非典型分枝杆菌感染中的用途。本发明还涉及包含上述化合物中至少一种和可选通过EthA途径激活的抗生素作为活性成分的药物组合物。

  公开号：

  US20150225388A1

文献信息

• Ligand Efficiency Driven Design of New Inhibitors of <i>Mycobacterium tuberculosis</i> Transcriptional Repressor EthR Using Fragment Growing, Merging, and Linking Approaches
  作者：Baptiste Villemagne、Marion Flipo、Nicolas Blondiaux、Céline Crauste、Sandra Malaquin、Florence Leroux、Catherine Piveteau、Vincent Villeret、Priscille Brodin、Bruno O. Villoutreix、Olivier Sperandio、Sameh H. Soror、Alexandre Wohlkönig、René Wintjens、Benoit Deprez、Alain R. Baulard、Nicolas Willand

  DOI：10.1021/jm500422b

  日期：2014.6.12

  Tuberculosis remains a major cause of mortality and morbidity, killing each year more than one million people. Although the combined use of first line antibiotics (isoniazid, rifampicin, pyrazinamide, and ethambutol) is efficient to treat most patients, the rapid emergence of multidrug resistant strains of Mycobacterium tuberculosis stresses the need for alternative therapies. Mycobacterial transcriptional repressor EthR is a key player in the control of second-line drugs bioactivation such as ethionamide and has been shown to impair the sensitivity of the human pathogen Mycobacterium tuberculosis to this antibiotic. As a way to identify new potent ligands of this protein, we have developed fragment-based approaches. In the current study, we combined surface plasmon resonance assay, X-ray crystallography, and ligand efficiency driven design for the rapid discovery and optimization of new chemotypes of EthR ligands starting from a fragment. The design, synthesis, and in vitro and ex vivo activities of these compounds will be discussed.
• COMPOSES UTILISABLES DANS LE TRAITEMENT DES INFECTIONS MYCOBACTERIENNES
  申请人：Université de Droit et de la Santé de Lille 2

  公开号：EP2900638A1

  公开（公告）日：2015-08-05
• US9920042B2
  申请人：——

  公开号：US9920042B2

  公开（公告）日：2018-03-20