(3RS,3aSR,6aRS)-2-methyl-3-(pyren-1-yl)dihydro-2H-pyrrolo[3,4-d]isoxazole-4,6(5H,6aH)-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 芘
• 英文名称: (3RS,3aSR,6aRS)-2-methyl-3-(pyren-1-yl)dihydro-2H-pyrrolo[3,4-d]isoxazole-4,6(5H,6aH)-dione
• 英文别名: (3R,3aS,6aR)-2-methyl-3-pyren-1-yl-3a,6a-dihydro-3H-pyrrolo[3,4-d][1,2]oxazole-4,6-dione
• 化学式: C₂₂H₁₆N₂O₃
• 分子量: 356.381
• InChiKey: QWUXYUJJAWUEEM-SLFFLAALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  27
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-methyl-1-pyren-1-ylmethanimine oxide 、 马来酰亚胺 以 甲苯 为溶剂， 反应 18.0h， 生成 (3RS,3aSR,6aRS)-2-methyl-3-(pyren-1-yl)dihydro-2H-pyrrolo[3,4-d]isoxazole-4,6(5H,6aH)-dione 、 (3RS,3aRS,6aSR)-2-methyl-3-(pyren-1-yl)dihydro-2H-pyrrolo[3,4-d]isoxazole-4,6(5H,6aH)-dione
  参考文献：
  名称：

  Isoxazolidinyl polycyclic aromatic hydrocarbons as DNA-intercalating antitumor agents

  摘要：

  The second generation and an isosteric series of isoxazolidinyl polycyclic aromatic hydrocarbons, as DNA-intercalator agents designed to act on remotely implanted tumors, have been synthesized in good yields according to the 1,3-dipolar cycloaddition methodology. The structure of the obtained cyclo-adducts has been determined by NOE experiments and supported by computational studies at PM3 level. The utility of this new template in the synthesis of structures designed to capitalize on its intercalative properties has been examined. All the obtained compounds have been tested for their in vitro cytotoxic activity and the most potent of them showed an IC50 of 9 mu M upon the human lung cancer (A-549) cell and a binding constant, for the intercalation with calf thymus DNA, of 9.6 x 10(4) M-1. Biological and docking studies showed that these compounds complex exclusively by intercalation between base pairs, approaching the DNA from its minor groove, with a neat selectivity for the AT or GC nucleobases. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.10.023

文献信息

• Isoxazolidinyl polycyclic aromatic hydrocarbons as DNA-intercalating antitumor agents
  作者：Antonio Rescifina、Ugo Chiacchio、Antonino Corsaro、Anna Piperno、Roberto Romeo

  DOI：10.1016/j.ejmech.2010.10.023

  日期：2011.1

  The second generation and an isosteric series of isoxazolidinyl polycyclic aromatic hydrocarbons, as DNA-intercalator agents designed to act on remotely implanted tumors, have been synthesized in good yields according to the 1,3-dipolar cycloaddition methodology. The structure of the obtained cyclo-adducts has been determined by NOE experiments and supported by computational studies at PM3 level. The utility of this new template in the synthesis of structures designed to capitalize on its intercalative properties has been examined. All the obtained compounds have been tested for their in vitro cytotoxic activity and the most potent of them showed an IC50 of 9 mu M upon the human lung cancer (A-549) cell and a binding constant, for the intercalation with calf thymus DNA, of 9.6 x 10(4) M-1. Biological and docking studies showed that these compounds complex exclusively by intercalation between base pairs, approaching the DNA from its minor groove, with a neat selectivity for the AT or GC nucleobases. (C) 2010 Elsevier Masson SAS. All rights reserved.