1-(4-methoxyphenyl)-6-[4-(methylamino)phenyl]-3-(trifluoromethyl)-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridin-7-one | 959426-74-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-methoxyphenyl)-6-[4-(methylamino)phenyl]-3-(trifluoromethyl)-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridin-7-one
• 英文别名: 1-(4-methoxyphenyl)-6-[4-(methylamino)phenyl]-3-(trifluoromethyl)-4,5-dihydropyrazolo[3,4-c]pyridin-7-one
• CAS: 959426-74-5
• 化学式: C₂₁H₁₉F₃N₄O₂
• 分子量: 416.403
• InChiKey: LRJGICFBUGSISP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(4-methoxyphenyl)-6-[4-(methylamino)phenyl]-3-(trifluoromethyl)-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridin-7-one 、 碘甲烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以47%的产率得到6-[4-(dimethylamino)phenyl]-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridin-7-one
  参考文献：
  名称：

  Discovery of 1-(4-Methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro- 1H-pyrazolo[3,4-c]pyridine-3-carboxamide (Apixaban, BMS-562247), a Highly Potent, Selective, Efficacious, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa

  摘要：

  Efforts to identify a suitable follow-on compound to razaxaban (compound 4) focused on modification of the carboxamido linker to eliminate potential in vivo hydrolysis to a primary aniline. Cyclization of the carboxamido linker to the novel bicyclic tetrahydropyrazolopyridinone scaffold retained the potent fXa binding activity. Exceptional potency of the series prompted an investigation of the neutral P-1 moieties that resulted in the identification of the p-methoxyphenyl P-1, which retained factor Xa binding affinity and good oral bioavailability. Further optimization of the C-3 pyrazole position and replacement of the terminal P-4 ring with a neutral heterocycle culminated in the discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidinl-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, compound 40). Compound 40 exhibits a high degree of fXa potency, selectivity, and efficacy and has an improved pharmacokinetic profile relative to 4.

  DOI：

  10.1021/jm070245n
• 作为产物：
  描述：

  tert-butyl 4-(1-(4-methoxyphenyl)-7-oxo-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)phenyl(methyl)carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 1-(4-methoxyphenyl)-6-[4-(methylamino)phenyl]-3-(trifluoromethyl)-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridin-7-one
  参考文献：
  名称：

  Glycinamides as factor Xa inhibitors

  摘要：

  本申请描述了甘氨酰胺化合物及其衍生物，或其药用可接受的盐形式，这些化合物可作为因子Xa的抑制剂。

  公开号：

  US20030232804A1