7-(Difluoromethyl)-5-phenylpyrazolo[1,5-a]pyrimidine-3-carbonyl chloride | 861412-81-9

• 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: 7-(Difluoromethyl)-5-phenylpyrazolo[1,5-a]pyrimidine-3-carbonyl chloride
• CAS: 861412-81-9
• 化学式: C₁₄H₈ClF₂N₃O
• 分子量: 307.687
• InChiKey: GHMRATQJEXMGOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  47.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-(Difluoromethyl)-5-phenylpyrazolo[1,5-a]pyrimidine-3-carbonyl chloride 、 2-氨基-5,6-二氢-环戊烷并噻吩-3-羰酰胺 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以69%的产率得到N-(3-carbamoyl-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)-7-(difluoromethyl)-5-phenylpyrazolo[1,5-a]pyrimidine-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：

  4,4-二氟-1-苯基-1,3-丁二酮 在 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 5.0h， 生成 7-(Difluoromethyl)-5-phenylpyrazolo[1,5-a]pyrimidine-3-carbonyl chloride
  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