2-((6-methoxy-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)methyl)-7-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline | 1610624-89-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-((6-methoxy-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)methyl)-7-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline
• CAS: 1610624-89-9
• 化学式: C₂₅H₂₃F₃N₄O
• 分子量: 452.479
• InChiKey: HJCPJRMRQGOEEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.31
• 重原子数：
  33.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  43.18
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-((6-methoxy-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)methyl)-7-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline 在 碘代三甲硅烷 作用下， 以 乙腈 为溶剂， 反应 1.0h， 生成 3-methyl-1-phenyl-5-((7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl)methyl)-1H-pyrazolo[3,4-b]pyridin-6(7H)-one
  参考文献：
  名称：

  Discovery of Pyrazolopyridones as a Novel Class of Noncovalent DprE1 Inhibitor with Potent Anti-Mycobacterial Activity

  摘要：

  A novel pyrazolopyridone class of inhibitors was identified from whole cell screening against Mycobacterium tuberculosis (Mtb). The series exhibits excellent bactericidality in vitro, resulting in a 4 log reduction in colony forming units following compound exposure. The significant modulation of minimum inhibitory concentration (MIC) against a Mtb strain overexpressing the Rv3790 gene suggested the target of pyrazolopyridones to be decaprenylphosphoryl-beta-D-ribose-2'-epimerase (DprE1). Genetic mapping of resistance mutation coupled with potent enzyme inhibition activity confirmed the molecular target. Detailed biochemical characterization revealed the series to be a noncovalent inhibitor of DprE1. Docking studies at the active site suggest that the series can be further diversified to improve the physicochemical properties without compromising the antimycobacterial activity. The pyrazolopyridone class of inhibitors offers an attractive non-nitro lead series targeting the essential and vulnerable DprE1 enzyme for the discovery of novel antimycobacterial agents to treat both drug susceptible and drug resistant strains of Mtb.

  DOI：

  10.1021/jm5002937
• 作为产物：
  描述：

  (6-methoxy-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)methanol 在 三溴化磷 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 2-((6-methoxy-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)methyl)-7-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Discovery of Pyrazolopyridones as a Novel Class of Noncovalent DprE1 Inhibitor with Potent Anti-Mycobacterial Activity

  摘要：

  A novel pyrazolopyridone class of inhibitors was identified from whole cell screening against Mycobacterium tuberculosis (Mtb). The series exhibits excellent bactericidality in vitro, resulting in a 4 log reduction in colony forming units following compound exposure. The significant modulation of minimum inhibitory concentration (MIC) against a Mtb strain overexpressing the Rv3790 gene suggested the target of pyrazolopyridones to be decaprenylphosphoryl-beta-D-ribose-2'-epimerase (DprE1). Genetic mapping of resistance mutation coupled with potent enzyme inhibition activity confirmed the molecular target. Detailed biochemical characterization revealed the series to be a noncovalent inhibitor of DprE1. Docking studies at the active site suggest that the series can be further diversified to improve the physicochemical properties without compromising the antimycobacterial activity. The pyrazolopyridone class of inhibitors offers an attractive non-nitro lead series targeting the essential and vulnerable DprE1 enzyme for the discovery of novel antimycobacterial agents to treat both drug susceptible and drug resistant strains of Mtb.

  DOI：

  10.1021/jm5002937