N-[(1E)-(5-bromo-2-methoxyphenyl)methylene]-2-{[(1-methyl-1H-pyrrol-2-yl)sulfonyl]methyl}aniline | 1392510-52-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-[(1E)-(5-bromo-2-methoxyphenyl)methylene]-2-{[(1-methyl-1H-pyrrol-2-yl)sulfonyl]methyl}aniline
• CAS: 1392510-52-9
• 化学式: C₂₀H₁₉BrN₂O₃S
• 分子量: 447.352
• InChiKey: PKIYDFXGFXMWIR-LPYMAVHISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.52
• 重原子数：
  27.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  60.66
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  甲基硝基苯 在 ferrous(II) sulfate heptahydrate 、 ammonium hydroxide 、 sodium tetrahydroborate 、 potassium peroxymonosulfate 、 N-溴代丁二酰亚胺(NBS) 、 溶剂黄146 、 sodium sulfate 、 过氧化苯甲酰 作用下， 以 甲醇 、 四氯化碳 、 乙醇 、 水 、 异丙醇 为溶剂， 反应 15.83h， 生成 N-[(1E)-(5-bromo-2-methoxyphenyl)methylene]-2-{[(1-methyl-1H-pyrrol-2-yl)sulfonyl]methyl}aniline
  参考文献：
  名称：

  Synthesis and Study of 2-(Pyrrolesulfonylmethyl)-N-arylimines: A New Class of Inhibitors for Human Glutathione Transferase A1-1

  摘要：

  Overexpression of human GSTA1-1 in tumor cells is part of MDR mechanisms. We report on the synthesis of 11 pyrrole derivatives as hGSTA1-1 inhibitors starting from 1-methyl-2-[(2-nitrobenzylsulfanyl]-1H-pyrrole. Molecular modeling revealed two locations in the enzyme H binding site: the catalytic primary one accommodating shorter and longer derivatives and the secondary one, where shorter derivatives can occupy. Derivative 9, displaying the highest inhibition and bearing a p-nitroarylimino moiety, and derivative 4, lacking this moiety, were studied kinetically. Derivative 9 binds (K-i(9) = 71 +/- 4 mu M) at the primary site competitively vs CDNB. Derivative 4 binds (K-i(4) = 135 +/- 27 mu m) at the primary and secondary sites, allowing the binding of a second molecule (4 or CDNB) leading to formation of unreactive and reactive complexes, respectively. The arylmethylsulfonylpyrrole core structure is a new pharmacophore for hGSTA1-1, whereas its derivative 9 may serve as a lead structure.

  DOI：

  10.1021/jm300385f

文献信息

• Synthesis and Study of 2-(Pyrrolesulfonylmethyl)-<i>N</i>-arylimines: A New Class of Inhibitors for Human Glutathione Transferase A1-1
  作者：Georgia E. Koutsoumpli、Virginia D. Dimaki、Trias N. Thireou、Elias E. Eliopoulos、Nikolaos E. Labrou、George I. Varvounis、Yannis D. Clonis

  DOI：10.1021/jm300385f

  日期：2012.8.9

  Overexpression of human GSTA1-1 in tumor cells is part of MDR mechanisms. We report on the synthesis of 11 pyrrole derivatives as hGSTA1-1 inhibitors starting from 1-methyl-2-[(2-nitrobenzylsulfanyl]-1H-pyrrole. Molecular modeling revealed two locations in the enzyme H binding site: the catalytic primary one accommodating shorter and longer derivatives and the secondary one, where shorter derivatives can occupy. Derivative 9, displaying the highest inhibition and bearing a p-nitroarylimino moiety, and derivative 4, lacking this moiety, were studied kinetically. Derivative 9 binds (K-i(9) = 71 +/- 4 mu M) at the primary site competitively vs CDNB. Derivative 4 binds (K-i(4) = 135 +/- 27 mu m) at the primary and secondary sites, allowing the binding of a second molecule (4 or CDNB) leading to formation of unreactive and reactive complexes, respectively. The arylmethylsulfonylpyrrole core structure is a new pharmacophore for hGSTA1-1, whereas its derivative 9 may serve as a lead structure.