2-({[5-phenyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]-carbonyl}amino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide | 848431-85-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-({[5-phenyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]-carbonyl}amino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide
• 英文别名: N-(3-carbamoyl-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)-5-phenyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide
• CAS: 848431-85-6
• 化学式: C₂₃H₁₈F₃N₅O₂S
• 分子量: 485.489
• InChiKey: USEDCWWUUOSLOT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  131
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  苯甲酰三氟丙酮 在 吡啶 、 草酰氯 、 溶剂黄146 、 N,N-二甲基甲酰胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 21.0h， 生成 2-({[5-phenyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]-carbonyl}amino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide
  参考文献：
  名称：

  Optimization of Small-Molecule Inhibitors of Influenza Virus Polymerase: From Thiophene-3-Carboxamide to Polyamido Scaffolds

  摘要：

  Influenza virus infections represent a serious concern to public health, being characterized by high morbidity and significant mortality. To date, compounds targeting the viral ion-channel M2 or the viral neuraminidase are the drugs available for treatment of influenza, but the emergence of drug-resistant viral mutants renders the search for novel targets and their possible inhibitors a major priority. Recently, we I I demonstrated that the viral RNA-dependent RNA polymerase (RdRP) complex can be an optimal target of protein protein disruption by small molecules, with thiophene-3-carboxamide derivatives emerging as promising candidates for the development of new anti-influenza drugs with broad-spectrum activity. Here, we report a further dissection of the thiophene-3-carboxamide structure. By using a GRID molecular interaction field (MIF)-based scaffold-hopping approach, more potent and nontoxic polyamido derivatives were identified, highlighting a new space in the chemical variability of RdRP inhibitors. Finally, a possible pharmacophoric model highlighting the key features required for RdRP inhibition is proposed.

  DOI：

  10.1021/jm500300r

文献信息

• Optimization of Small-Molecule Inhibitors of Influenza Virus Polymerase: From Thiophene-3-Carboxamide to Polyamido Scaffolds
  作者：Susan Lepri、Giulio Nannetti、Giulia Muratore、Gabriele Cruciani、Renzo Ruzziconi、Beatrice Mercorelli、Giorgio Palù、Arianna Loregian、Laura Goracci

  DOI：10.1021/jm500300r

  日期：2014.5.22

  Influenza virus infections represent a serious concern to public health, being characterized by high morbidity and significant mortality. To date, compounds targeting the viral ion-channel M2 or the viral neuraminidase are the drugs available for treatment of influenza, but the emergence of drug-resistant viral mutants renders the search for novel targets and their possible inhibitors a major priority. Recently, we I I demonstrated that the viral RNA-dependent RNA polymerase (RdRP) complex can be an optimal target of protein protein disruption by small molecules, with thiophene-3-carboxamide derivatives emerging as promising candidates for the development of new anti-influenza drugs with broad-spectrum activity. Here, we report a further dissection of the thiophene-3-carboxamide structure. By using a GRID molecular interaction field (MIF)-based scaffold-hopping approach, more potent and nontoxic polyamido derivatives were identified, highlighting a new space in the chemical variability of RdRP inhibitors. Finally, a possible pharmacophoric model highlighting the key features required for RdRP inhibition is proposed.