3-[4-[4-[(2S,6R)-2,6-dimethylpiperidin-1-yl]butyl]-3-oxo-1,4-benzoxazin-2-yl]benzonitrile | 1027220-19-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 3-[4-[4-[(2S,6R)-2,6-dimethylpiperidin-1-yl]butyl]-3-oxo-1,4-benzoxazin-2-yl]benzonitrile
• CAS: 1027220-19-4
• 化学式: C₂₆H₃₁N₃O₂
• 分子量: 417.551
• InChiKey: PXKWWXKMUOYYFU-WPUZRXDDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  56.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[4-[4-[(2S,6R)-2,6-dimethylpiperidin-1-yl]butyl]-3-oxo-1,4-benzoxazin-2-yl]benzonitrile 在 盐酸羟胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 [(Z)-[amino-[3-[4-[4-[(2R,6S)-2,6-dimethylpiperidin-1-yl]butyl]-3-oxo-1,4-benzoxazin-2-yl]phenyl]methylidene]amino] 2,2,2-trifluoroacetate
  参考文献：
  名称：

  Rational Design, Synthesis, and Biological Activity of Benzoxazinones as Novel Factor Xa Inhibitors

  摘要：

  Inappropriate thrombus formation within blood vessels is the leading cause of mortality in the industrialized world. Factor Xa (FXa) is a trypsin-like serine protease that plays a key role in the blood coagulation cascade and represents an attractive target for anticoagulant drug development, From a high-throughput in vitro mass screen of our chemical library, we identified 4-[5-[(2R,6S)-2,6-dimethyltetrahydro-1(2H)-pyridinyl]pentyl]-2-phenyl-2H-1,4-benzoxazin-3(4H)-one (1a) as an inhibitor of FXa with an IC50 of 27 muM. Through a combination of SAR studies and molecular modeling, we synthesized 3-(4-[5-[(2R,6S)-2,6-dimethyltetrahydro-1(2N)-pyridinyl]pentyl]-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl)-1-benzenecarboximidamide (1n) which was a potent FXa inhibitor with an IC50 of 3 nM. This compound exhibited high selectivity for FXa over other related serine proteases and was efficacious when dosed intravenously in rabbit and dog antithrombotic models.

  DOI：

  10.1021/jm000074l
• 作为产物：
  描述：

  2-溴-2-(3-溴苯基)乙酸甲酯 在 四(三苯基膦)钯 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 3-[4-[4-[(2S,6R)-2,6-dimethylpiperidin-1-yl]butyl]-3-oxo-1,4-benzoxazin-2-yl]benzonitrile
  参考文献：
  名称：

  Rational Design, Synthesis, and Biological Activity of Benzoxazinones as Novel Factor Xa Inhibitors

  摘要：

  Inappropriate thrombus formation within blood vessels is the leading cause of mortality in the industrialized world. Factor Xa (FXa) is a trypsin-like serine protease that plays a key role in the blood coagulation cascade and represents an attractive target for anticoagulant drug development, From a high-throughput in vitro mass screen of our chemical library, we identified 4-[5-[(2R,6S)-2,6-dimethyltetrahydro-1(2H)-pyridinyl]pentyl]-2-phenyl-2H-1,4-benzoxazin-3(4H)-one (1a) as an inhibitor of FXa with an IC50 of 27 muM. Through a combination of SAR studies and molecular modeling, we synthesized 3-(4-[5-[(2R,6S)-2,6-dimethyltetrahydro-1(2N)-pyridinyl]pentyl]-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl)-1-benzenecarboximidamide (1n) which was a potent FXa inhibitor with an IC50 of 3 nM. This compound exhibited high selectivity for FXa over other related serine proteases and was efficacious when dosed intravenously in rabbit and dog antithrombotic models.

  DOI：

  10.1021/jm000074l