11-cyano-2,3-dimethylisoindolo[2,1-a]quinoxaline | 1018073-86-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 11-cyano-2,3-dimethylisoindolo[2,1-a]quinoxaline
• 英文别名: 11-cyano-2,3-dimethyl-isoindolo[2,1-a]quinoxaline；2,3-Dimethylisoindolo[2,3-a]quinoxaline-11-carbonitrile
• CAS: 1018073-86-3
• 化学式: C₁₈H₁₃N₃
• 分子量: 271.321
• InChiKey: BKMJSOJBPVYNSI-UHFFFAOYSA-N

物化性质

• 熔点：
  220-221 °C
• 密度：
  1.23±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  41.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-cyano-2-(2'-amino-4',5'-dimethylphenyl)isoindole 、 甲酸 以71%的产率得到11-cyano-2,3-dimethylisoindolo[2,1-a]quinoxaline
  参考文献：
  名称：

  Isoindolo[2,1-a]quinoxaline Derivatives, Novel Potent Antitumor Agents with Dual Inhibition of Tubulin Polymerization and Topoisomerase I

  摘要：

  Isoindoloquinoxalines 4 and 5 were obtained by refluxing 2-(2'-aminoaryl)-1-cyanoisoindoles 3a-e in acetic or formic acid. All derivatives were screened by the National Cancer Institute (Bethesda, MD) for the in vitro one dose primary anticancer assay against a 3-cell line panel. Compounds 4a-e, screened against a panel of about 60 human tumor cell lines, showed remarkable antineoplastic activity; they had GI(50) values in the low micromolar or submicromolar range and reached, in the case of 4c, nanomolar concentrations on 88% of the 59 tested cell lines. Flow cytometric analysis of cell cycle after treatment with 4c demonstrated an arrest of the cell cycle in G2/M phase. This effect was accompanied with apoptosis of the cells, mitochondrial depolarization, generation of reactive oxygen species, and activation of caspase-3 and caspase-9. Moreover, 4c induced a clear increase in the mitotic index, inhibited microtubule assembly in vitro, and interestingly also acted as a topoisomerase I inhibitor.

  DOI：

  10.1021/jm070834t

文献信息

• WO2008/41264
  申请人：——

  公开号：——

  公开（公告）日：——
• Isoindolo[2,1-<i>a</i>]quinoxaline Derivatives, Novel Potent Antitumor Agents with Dual Inhibition of Tubulin Polymerization and Topoisomerase I
  作者：Patrizia Diana、Annamaria Martorana、Paola Barraja、Alessandra Montalbano、Gaetano Dattolo、Girolamo Cirrincione、Francesco Dall’Acqua、Alessia Salvador、Daniela Vedaldi、Giuseppe Basso、Giampietro Viola

  DOI：10.1021/jm070834t

  日期：2008.4.1

  Isoindoloquinoxalines 4 and 5 were obtained by refluxing 2-(2'-aminoaryl)-1-cyanoisoindoles 3a-e in acetic or formic acid. All derivatives were screened by the National Cancer Institute (Bethesda, MD) for the in vitro one dose primary anticancer assay against a 3-cell line panel. Compounds 4a-e, screened against a panel of about 60 human tumor cell lines, showed remarkable antineoplastic activity; they had GI(50) values in the low micromolar or submicromolar range and reached, in the case of 4c, nanomolar concentrations on 88% of the 59 tested cell lines. Flow cytometric analysis of cell cycle after treatment with 4c demonstrated an arrest of the cell cycle in G2/M phase. This effect was accompanied with apoptosis of the cells, mitochondrial depolarization, generation of reactive oxygen species, and activation of caspase-3 and caspase-9. Moreover, 4c induced a clear increase in the mitotic index, inhibited microtubule assembly in vitro, and interestingly also acted as a topoisomerase I inhibitor.