ethyl 7-(difluoromethyl)-5-phenylpyrazolo[1,5-a]pyrimidine-3-carboxylate

• 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: ethyl 7-(difluoromethyl)-5-phenylpyrazolo[1,5-a]pyrimidine-3-carboxylate
• 英文别名: ethyl 7-difluoromethyl-5-phenylpyrazolo[1,5-a]pyrimidine-3-carboxylate
• 化学式: C₁₆H₁₃F₂N₃O₂
• mdl: MFCD02253789
• 分子量: 317.295
• InChiKey: AZESOZJHNZZYFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  56.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 7-(difluoromethyl)-5-phenylpyrazolo[1,5-a]pyrimidine-3-carboxylate 在 草酰氯 、 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
• 作为产物：
  描述：

  4,4-二氟-1-苯基-1,3-丁二酮 、 3-氨基-4-乙氧羰基吡唑 在 溶剂黄146 作用下， 以71%的产率得到ethyl 7-(difluoromethyl)-5-phenylpyrazolo[1,5-a]pyrimidine-3-carboxylate
  参考文献：
  名称：

  5-二氟甲基和7-二氟甲基取代的吡唑并[1,5-a]嘧啶的区域选择性合成

  摘要：

  3,4-取代的5-氨基吡唑与含有二氟甲基的不对称1,3-二羰基化合物在乙酸中环缩合生成7-二氟甲基吡唑并[1,5- a ]嘧啶，而5-二氟甲基吡唑并[1,5- a] ]嘧啶衍生物主要在三氟乙酸中形成。

  DOI：

  10.1007/s10593-023-03236-5

文献信息

• ——
  作者：V. I. Filyakova、O. A. Kuznetsova、E. N. Ulomskii、T. V. Rybalova、Yu. V. Gatilov、M. I. Kodess、V. L. Rusinov、K. I. Pashkevich

  DOI：10.1023/a:1015420130033

  日期：——

  The reactions of Li enolates of fluorine-containing beta-diketones with 3-aminopyrazoles afforded (7-polyfluoroalkyl)pyrazolo[1,5-a]pyrimidines. The structure of 3-bromo-2-methyl-5-phenyl-7-trifluoromethylpyrazolo[1,5-a]pyrimidine was established by X-ray diffraction analysis.
• 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.
• A regioselective synthesis of 5-difluoromethyl- and 7-difluoromethyl-substituted pyrazolo[1,5-a]pyrimidines
  作者：Valery S. Tolkunov、Andrew S. Tolkunov、Olga V. Smirnova、Sergei V. Tolkunov

  DOI：10.1007/s10593-023-03236-5

  日期：2023.8

  cyclocondensation of 3,4-substituted 5-aminopyrazoles with unsymmetrical 1,3-dicarbonyl compounds containing the difluoromethyl group in acetic acid led to 7-difluoromethylpyrazolo[1,5-a]pyrimidines, whereas 5-difluoromethylpyrazolo[1,5-a]pyrimidine derivatives were predominantly formed in trifluoroacetic acid.

  3,4-取代的5-氨基吡唑与含有二氟甲基的不对称1,3-二羰基化合物在乙酸中环缩合生成7-二氟甲基吡唑并[1,5- a ]嘧啶，而5-二氟甲基吡唑并[1,5- a] ]嘧啶衍生物主要在三氟乙酸中形成。