11-cyano-2,3-dichloroisoindolo[2,1-a]quinoxaline | 1018073-88-5

• 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-dichloroisoindolo[2,1-a]quinoxaline
• 英文别名: 11-cyano-2,3-dichloro-isoindolo[2,1-a]quinoxaline；2,3-Dichloroisoindolo[2,3-a]quinoxaline-11-carbonitrile
• CAS: 1018073-88-5
• 化学式: C₁₆H₇Cl₂N₃
• 分子量: 312.158
• InChiKey: BQRVFGCEMOQEDQ-UHFFFAOYSA-N

物化性质

• 熔点：
  279-281 °C
• 密度：
  1.50±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 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'-dichlorophenyl)isoindole 、 甲酸 以75%的产率得到11-cyano-2,3-dichloroisoindolo[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：——
• [EN] ISOINDOLO-QUINOXALINE DERIVATIVES HAVING ANTITUMOR ACTIVITY, PROCESS FOR THEIR PRODUCTION AND THEIR USE<br/>[FR] DÉRIVÉS D'ISOINDOLOQUINOXALINE À ACTIVITÉ ANTITUMORALE, LEUR PROCÉDÉ DE PRODUCTION ET LEUR UTILISATION
  申请人：UNIV PALERMO

  公开号：WO2008041264A1

  公开（公告）日：2008-04-10

  [EN] New isoindolo[2,1-a]quinoxaline derivatives of general formula (1 ), wherein R represents H or OH and R₅ represents H or CN, have been prepared with simple procedures starting from known intermediates and resulted to posses potent in vitro antitumor activity against a panel of about 60 different human tumor cell lines belonging to several kinds of tumors, both hematological and solid. Preparations containing such derivatives as active ingredients are proposed as drugs to be employed in cancer therapy both alone and in combination with other chemotherapeutics.
  [FR] La présente invention concerne de nouveaux dérivés d'isoindolo[2,1-a]quinoxaline de formule générale (1 ), R représentant H ou OH et R₅ représentant H ou CN. Préparés à l'aide de procédés simples, au départ d'intermédiaires bien connus, les dérivés présentent une puissante activité antitumorale in vitro contre une série d'environ 60 lignées cellulaires tumorales humaines différentes appartenant à plusieurs types de tumeurs, tant hématologiques que solides. Les préparations selon l'invention, qui contiennent de tels dérivés en tant que principes actifs, peuvent servir de médicaments à des fins thérapeutiques anticancéreuses, tant individuellement que combinées à d'autres substances chimiothérapeutiques.
• 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.