6-(4-iodophenyl)-1-(4-methoxyphenyl)-N-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide | 959426-36-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-(4-iodophenyl)-1-(4-methoxyphenyl)-N-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide
• 英文别名: 6-(4-iodophenyl)-1-(4-methoxyphenyl)-N-methyl-7-oxo-4,5-dihydropyrazolo[3,4-c]pyridine-3-carboxamide
• CAS: 959426-36-9
• 化学式: C₂₁H₁₉IN₄O₃
• 分子量: 502.311
• InChiKey: IEZXWTUPMMGWSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  76.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(4-iodophenyl)-1-(4-methoxyphenyl)-N-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide 、 2-甲酰基苯硼酸 在 四(三苯基膦)钯 potassium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 24.0h， 以79%的产率得到6-(2'-formylbiphenyl-4-yl)-1-(4-methoxyphenyl)-N-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide
  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：

  6-(4-碘苯基)-1-(4-甲氧基苯基)-7-氧代-4,5,6,7-四氢-1H-吡唑并[3,4-c]吡啶-3-羧酸 、 甲胺 在 三甲基铝 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 72.25h， 以92%的产率得到6-(4-iodophenyl)-1-(4-methoxyphenyl)-N-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide
  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