N-(5-(4-chloro-3-(N-(4-fluorophenyl)sulfamoyl)phenyl)-4-methylthiazol-2-yl)acetamide | 1429628-39-6

• 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: N-(5-(4-chloro-3-(N-(4-fluorophenyl)sulfamoyl)phenyl)-4-methylthiazol-2-yl)acetamide
• 英文别名: PT420；N-[5-[4-chloro-3-[(4-fluorophenyl)sulfamoyl]phenyl]-4-methyl-1,3-thiazol-2-yl]acetamide
• CAS: 1429628-39-6
• 化学式: C₁₈H₁₅ClFN₃O₃S₂
• 分子量: 439.919
• InChiKey: NSZMXUXTPZEXIU-UHFFFAOYSA-N

物化性质

• 密度：
  1.506±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氯-5-(2-氧代丙基)苯磺酰氯 在 tribromure de carboxyethyl-2 triphenylphosphonium 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 1.5h， 生成 N-(5-(4-chloro-3-(N-(4-fluorophenyl)sulfamoyl)phenyl)-4-methylthiazol-2-yl)acetamide
  参考文献：
  名称：

  磷脂酰肌醇4激酶IIIβ的有效和选择性抑制剂的设计和结构表征

  摘要：

  III型磷脂酰肌醇4激酶（PI4KIIIβ）是介导膜运输的必不可少的酶，与多种致病过程有关。它是介导RNA病毒复制的关键宿主因子。该酶的有效和特异性抑制剂的设计对于定义其细胞作用至关重要，并可能导致新型抗病毒治疗。我们先前曾报道过PI4K抑制剂PIK93，并且该化合物具有PI4KIIIβ的关键功能。然而，该化合物显示出与I和III类PI3K的高交叉反应性。使用基于结构的药物设计，我们设计了新颖的有效和选择性（比I和III类PI3K高1000倍以上）的PI4KIIIβ抑制剂。这些化合物显示出抗丙型肝炎病毒的抗病毒活性。与最有效的化合物之一结合的PI4KIIIβ的共晶体结构揭示了特异性的分子基础。这项工作对于新型PI4KIIIβ抑制剂的设计至关重要，而PI4KIIIβ抑制剂可能起着重要的抗病毒治疗作用。

  DOI：

  10.1021/acs.jmedchem.5b01311

文献信息

• PI-kinase Inhibitors with Broad Spectrum Anti-Infective Activity
  申请人：The Regents of the University of California

  公开号：US20150051193A1

  公开（公告）日：2015-02-19

  Compounds and methods are provided for the treatment of pathogen infections. In some embodiments, the anti-infective compounds have broad spectrum activity against a variety of infective diseases, where the diseases are caused by pathogens containing a basic amino acid PIP-2 pincer (BAAPP) domain that interacts with phosphatidylinositol 4,5-bisphosphate (PIP-2) to mediate pathogen replication. Also provided are methods of inhibiting a PI4-kinase and methods of inhibiting viral infection. In some embodiments, the compound is a PI4-kinase inhibiting compound that is a 5-aryl-thiazole. The subject compounds may be formulated or provided to a subject in combination with a second anti-infective agent, e.g. interferon, ribivarin, and the like.
• US9309236B2
  申请人：——

  公开号：US9309236B2

  公开（公告）日：2016-04-12
• [EN] PI-KINASE INHIBITORS WITH BROAD SPECTRUM ANTI-INFECTIVE ACTIVITY<br/>[FR] INHIBITEURS DE PI-KINASE À ACTIVITÉ ANTI-INFECTIEUSE À LARGE SPECTRE
  申请人：UNIV LELAND STANFORD JUNIOR

  公开号：WO2013052845A1

  公开（公告）日：2013-04-11

  Compounds and methods are provided for the treatment of pathogen infections. In some embodiments, the anti-infective compounds have broad spectrum activity against a variety of infective diseases, where the diseases are caused by pathogens containing a basic amino acid PIP-2 pincer (BAAPP) domain that interacts with phosphatidylinositol 4,5-bisphosphate (PIP-2) to mediate pathogen replication. Also provided are methods of inhibiting a PI4-kinase and methods of inhibiting viral infection. In some embodiments, the compound is a PI4-kinase inhibiting compound that is a 5-aryl-thiazole. The subject compounds may be formulated or provided to a subject in combination with a second anti-infective agent, e.g. interferon, ribivarin, and the like.
• Design and Structural Characterization of Potent and Selective Inhibitors of Phosphatidylinositol 4 Kinase IIIβ
  作者：Florentine U. Rutaganira、Melissa L. Fowler、Jacob A. McPhail、Michael A. Gelman、Khanh Nguyen、Anming Xiong、Gillian L. Dornan、Brandon Tavshanjian、Jeffrey S. Glenn、Kevan M. Shokat、John E. Burke

  DOI：10.1021/acs.jmedchem.5b01311

  日期：2016.3.10

  viruses. The design of potent and specific inhibitors of this enzyme will be essential to define its cellular roles and may lead to novel antiviral therapeutics. We previously reported the PI4K inhibitor PIK93, and this compound has defined key functions of PI4KIIIβ. However, this compound showed high cross reactivity with class I and III PI3Ks. Using structure-based drug design, we have designed novel potent

  III型磷脂酰肌醇4激酶（PI4KIIIβ）是介导膜运输的必不可少的酶，与多种致病过程有关。它是介导RNA病毒复制的关键宿主因子。该酶的有效和特异性抑制剂的设计对于定义其细胞作用至关重要，并可能导致新型抗病毒治疗。我们先前曾报道过PI4K抑制剂PIK93，并且该化合物具有PI4KIIIβ的关键功能。然而，该化合物显示出与I和III类PI3K的高交叉反应性。使用基于结构的药物设计，我们设计了新颖的有效和选择性（比I和III类PI3K高1000倍以上）的PI4KIIIβ抑制剂。这些化合物显示出抗丙型肝炎病毒的抗病毒活性。与最有效的化合物之一结合的PI4KIIIβ的共晶体结构揭示了特异性的分子基础。这项工作对于新型PI4KIIIβ抑制剂的设计至关重要，而PI4KIIIβ抑制剂可能起着重要的抗病毒治疗作用。