3-bromo-4-[(4-methoxybenzyl)amino]thieno[3,2-c]pyridine-7-carbonitrile | 1529796-05-1

• 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: 3-bromo-4-[(4-methoxybenzyl)amino]thieno[3,2-c]pyridine-7-carbonitrile
• 英文别名: 3-Bromo-4-[(4-methoxyphenyl)methylamino]thieno[3,2-c]pyridine-7-carbonitrile；3-bromo-4-[(4-methoxyphenyl)methylamino]thieno[3,2-c]pyridine-7-carbonitrile
• CAS: 1529796-05-1
• 化学式: C₁₆H₁₂BrN₃OS
• 分子量: 374.261
• InChiKey: WHQRAAHZDHYZMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  86.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-bromo-4-[(4-methoxybenzyl)amino]thieno[3,2-c]pyridine-7-carbonitrile 在 四(三苯基膦)钯 、 sodium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 水 为溶剂， 反应 1.5h， 生成 4-(4-methoxybenzylamino)-3-(1H-pyrazol-5-yl)thieno[3,2-c]pyridine-7-carboxamide
  参考文献：
  名称：

  Identification through structure-based methods of a bacterial NAD+-dependent DNA ligase inhibitor that avoids known resistance mutations

  摘要：

  In an attempt to identify novel inhibitors of NAD(+)-dependent DNA ligase (LigA) that are not affected by a known resistance mutation in the adenosine binding pocket, a detailed analysis of the binding sites of a variety of bacterial ligases was performed. This analysis revealed several similarities to the adenine binding region of kinases, which enabled a virtual screen of known kinase inhibitors. From this screen, a thienopyridine scaffold was identified that was shown to inhibit bacterial ligase. Further characterization through structure and enzymology revealed the compound was not affected by a previously disclosed resistance mutation in Streptococcus pneumoniae LigA, Leu75Phe. A subsequent medicinal chemistry program identified substitutions that resulted in an inhibitor with moderate activity across various Gram-positive bacterial LigA enzymes. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.11.007
• 作为产物：
  描述：

  3-bromo-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-7-carbonitrile 在 potassium carbonate 、 三氯氧磷 作用下， 以 N-甲基吡咯烷酮 为溶剂， 生成 3-bromo-4-[(4-methoxybenzyl)amino]thieno[3,2-c]pyridine-7-carbonitrile
  参考文献：
  名称：

  Identification through structure-based methods of a bacterial NAD+-dependent DNA ligase inhibitor that avoids known resistance mutations

  摘要：

  In an attempt to identify novel inhibitors of NAD(+)-dependent DNA ligase (LigA) that are not affected by a known resistance mutation in the adenosine binding pocket, a detailed analysis of the binding sites of a variety of bacterial ligases was performed. This analysis revealed several similarities to the adenine binding region of kinases, which enabled a virtual screen of known kinase inhibitors. From this screen, a thienopyridine scaffold was identified that was shown to inhibit bacterial ligase. Further characterization through structure and enzymology revealed the compound was not affected by a previously disclosed resistance mutation in Streptococcus pneumoniae LigA, Leu75Phe. A subsequent medicinal chemistry program identified substitutions that resulted in an inhibitor with moderate activity across various Gram-positive bacterial LigA enzymes. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.11.007

文献信息

• Identification through structure-based methods of a bacterial NAD+-dependent DNA ligase inhibitor that avoids known resistance mutations
  作者：Kerry Murphy-Benenato、Hongming Wang、Helen M. McGuire、Hajnalka E. Davis、Ning Gao、D. Bryan Prince、Haris Jahic、Suzanne S. Stokes、P. Ann Boriack-Sjodin

  DOI：10.1016/j.bmcl.2013.11.007

  日期：2014.1

  In an attempt to identify novel inhibitors of NAD(+)-dependent DNA ligase (LigA) that are not affected by a known resistance mutation in the adenosine binding pocket, a detailed analysis of the binding sites of a variety of bacterial ligases was performed. This analysis revealed several similarities to the adenine binding region of kinases, which enabled a virtual screen of known kinase inhibitors. From this screen, a thienopyridine scaffold was identified that was shown to inhibit bacterial ligase. Further characterization through structure and enzymology revealed the compound was not affected by a previously disclosed resistance mutation in Streptococcus pneumoniae LigA, Leu75Phe. A subsequent medicinal chemistry program identified substitutions that resulted in an inhibitor with moderate activity across various Gram-positive bacterial LigA enzymes. (C) 2013 Elsevier Ltd. All rights reserved.