5-phenyl-7-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyrimidine-2-carboxylic acid | 312635-82-8

• 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: 5-phenyl-7-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyrimidine-2-carboxylic acid
• CAS: 312635-82-8
• 化学式: C₁₃H₇F₃N₄O₂
• 分子量: 308.219
• InChiKey: IGBPUIMKEZNOTP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  80.4
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-phenyl-7-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyrimidine-2-carboxylic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成
  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.