5-(4-Methoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carbonyl chloride | 848422-75-3

• 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-(4-Methoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carbonyl chloride
• CAS: 848422-75-3
• 化学式: C₁₅H₉ClF₃N₃O₂
• 分子量: 355.704
• InChiKey: GAQRZEOKZVGKRV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  56.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-(4-Methoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carbonyl chloride 、 2-氨基-4,5,6,7-四氢苯并[b]噻吩-3-甲酰胺 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以85%的产率得到2-({[5-(4-methoxyphenyl)-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
• 作为产物：
  描述：

  4,4,4-三氟-1-(4-甲氧基苯基)-1,3-丁烷二酮 在 N,N-二甲基甲酰胺 sodium hydroxide 、 草酰氯 、 乙醇 、 水 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 19.5h， 生成 5-(4-Methoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carbonyl chloride
  参考文献：
  名称：

  WO2008/134035

  摘要：

  公开号：

文献信息

• WO2008/134035
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.