2-amino-1-(2-fluorophenyl)-1H-pyrrolo[2,3-b]quinoxaline-3-carbonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2-amino-1-(2-fluorophenyl)-1H-pyrrolo[2,3-b]quinoxaline-3-carbonitrile
• 英文别名: 2-Amino-1-(2-fluorophenyl)pyrrolo[3,2-b]quinoxaline-3-carbonitrile
• 化学式: C₁₇H₁₀FN₅
• 分子量: 303.298
• InChiKey: OYDCOYMHSJGPKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-1-(2-fluorophenyl)-1H-pyrrolo[2,3-b]quinoxaline-3-carbonitrile 在 硫酸 作用下， 反应 0.5h， 以55%的产率得到2-amino-1-(2-fluorophenyl)-1H-pyrrolo[2,3-b]quinoxaline-3-carboxamide
  参考文献：
  名称：

  Pyrrolo[3,2-b]quinoxaline Derivatives as Types I_1/2 and II Eph Tyrosine Kinase Inhibitors: Structure-Based Design, Synthesis, and in Vivo Validation

  摘要：

  The X-ray crystal structures of the catalytic domain of the EphA3 tyrosine kinase in complex with two type I inhibitors previously discovered in silico (compounds A and B) were used to design type I-1/2 and II inhibitors. Chemical synthesis of about 25 derivatives culminated in the discovery of compounds 11d (type I-1/2), 7b, and 7g (both of type II), which have low-nanomolar affinity for Eph kinases in vitro and a good selectivity profile on a panel of 453 human kinases (395 nonmutant). Surface plasmon resonance measurements show a very slow unbinding rate (1/115 min) for inhibitor 7m. Slow dissociation is consistent with a type II binding mode in which the hydrophobic moiety (trifluoromethyl-benzene) of the inhibitor is deeply buried in a cavity originating from the displacement of the Phe side chain of the so-called DFG motif as observed in the crystal structure of compound 7m. The inhibitor 11d displayed good in vivo efficacy in a human breast cancer xenograft.

  DOI：

  10.1021/jm5009242
• 作为产物：
  描述：

  2,3-二氯喹喔啉 在 sodium hydride 作用下， 以 乙醇 、 甲苯 为溶剂， 生成 2-amino-1-(2-fluorophenyl)-1H-pyrrolo[2,3-b]quinoxaline-3-carbonitrile
  参考文献：
  名称：

  Pyrrolo[3,2-b]quinoxaline Derivatives as Types I_1/2 and II Eph Tyrosine Kinase Inhibitors: Structure-Based Design, Synthesis, and in Vivo Validation

  摘要：

  The X-ray crystal structures of the catalytic domain of the EphA3 tyrosine kinase in complex with two type I inhibitors previously discovered in silico (compounds A and B) were used to design type I-1/2 and II inhibitors. Chemical synthesis of about 25 derivatives culminated in the discovery of compounds 11d (type I-1/2), 7b, and 7g (both of type II), which have low-nanomolar affinity for Eph kinases in vitro and a good selectivity profile on a panel of 453 human kinases (395 nonmutant). Surface plasmon resonance measurements show a very slow unbinding rate (1/115 min) for inhibitor 7m. Slow dissociation is consistent with a type II binding mode in which the hydrophobic moiety (trifluoromethyl-benzene) of the inhibitor is deeply buried in a cavity originating from the displacement of the Phe side chain of the so-called DFG motif as observed in the crystal structure of compound 7m. The inhibitor 11d displayed good in vivo efficacy in a human breast cancer xenograft.

  DOI：

  10.1021/jm5009242