1-cyano-2-(2'-aminophenyl)isoindole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-cyano-2-(2'-aminophenyl)isoindole
• 英文别名: 2-(2-Aminophenyl)isoindole-1-carbonitrile
• 化学式: C₁₅H₁₁N₃
• 分子量: 233.272
• InChiKey: HWNOPPADMWZJNT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54.7
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-cyano-2-(2'-aminophenyl)isoindole 在 溶剂黄146 作用下， 反应 0.5h， 以99%的产率得到isoindolo[2,1-a]quinoxalin-6(5H)-one
  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
• 作为产物：
  描述：

  N-(2-aminophenyl)isoindole 、 氰化钾 以 水 为溶剂， 反应 1.5h， 生成 1-cyano-2-(2'-aminophenyl)isoindole
  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

• Isoindolo[2,1-c]benzo[1,2,4]triazines: A new ring system with antiproliferative activity
  作者：Patrizia Diana、Annamaria Martorana、Paola Barraja、Antonino Lauria、Alessandra Montalbano、Anna Maria Almerico、Gaetano Dattolo、Girolamo Cirrincione

  DOI：10.1016/j.bmc.2006.09.054

  日期：2007.1.1

  A series of isoindolo-benzo-triazines of type 4 was obtained by diazotization of 2-(2-aminoaryl)-1-cyanoisoindoles 3a-j. All the synthesized derivatives were screened by the National Cancer Institute (NCI, Bethesda, USA), for in vitro antitumor activity against a 3-human cancer cell line panel consisting of MCF7 (breast), NCI-H460 (lung), and SF-268 (CNS). Derivatives 4a, f, i, j were selected to be

  通过2-（2-氨基芳基）-1-氰基异吲哚3a-j的重氮化获得一系列类型4的异吲哚-苯并三嗪。美国国家癌症研究所（NCI，Bethesda，USA）对所有合成的衍生物进行了筛选，以针对由MCF7（乳腺癌），NCI-H460（肺）和SF- 268（CNS）。选择衍生物4a，f，i，j，以对来自九种人类癌细胞类型的约50种人类肿瘤细胞系进行全面评估，并通常在微摩尔范围内显示出抗增殖活性。最敏感的细胞系是：白血病亚组的MOLT-4和SR，非小细胞肺亚组的A549 / ATCC和EKVX，结肠癌亚组的COLO-205，黑素瘤亚组的LOX IMVI，OVCAR-8。卵巢癌子面板和MCF7，
• Water-soluble isoindolo[2,1-a]quinoxalin-6-imines: In vitro antiproliferative activity and molecular mechanism(s) of action
  作者：Barbara Parrino、Anna Carbone、Cristina Ciancimino、Virginia Spanò、Alessandra Montalbano、Paola Barraja、Girolamo Cirrincione、Patrizia Diana、Claudia Sissi、Manlio Palumbo、Odra Pinato、Marzia Pennati、Giovanni Beretta、Marco Folini、Peter Matyus、Balázs Balogh、Nadia Zaffaroni

  DOI：10.1016/j.ejmech.2015.03.005

  日期：2015.4

  Water-soluble isoindoloquinoxalin (IIQ) imines and the corresponding acetates were conveniently prepared from the key intermediates 2-(2'-aminophenyl)-2H-isoindole-1-carbonitriles obtained by a Strecker reaction between substituted 1,2-dicarbaldehydes and 1,2-phenylenediamines. Both series were screened by the National Cancer Institute (Bethesda, MD) and showed potent antiproliferative activity against a panel of 60 human tumor cell lines. Several of the novel compounds showed GI(50) values at a nanomolar level on the majority of the tested cell lines. Among IIQ derivatives, methoxy substituents at positions 3 and 8 or/and 9 were especially effective in impairing cell cycle progression and inducing apoptosis in cancer cells. These effects were associated to IIQ-mediated impairment of tubulin polymerization at pharmacologically significant concentrations of tested compounds. In addition, impaired DNA topoisomerase I functions and perturbation in telomere architecture were observed in cells exposed to micromolar concentrations of IIQ derivatives. The above results suggest that IIQ derivatives exhibit multi-target cytotoxic activities. (C) 2015 Elsevier Masson SAS. All rights reserved.
• WO2008/41264
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and evaluation of the antiproliferative activity of novel isoindolo[2,1-<i>a</i>]quinoxaline and indolo[1,2-<i>a</i>]quinoxaline derivatives
  作者：Vanessa Desplat、Stéphane Moreau、Solene Belisle-Fabre、Denis Thiolat、Juliette Uranga、Romain Lucas、Laure de Moor、Stéphane Massip、Christian Jarry、Djavad M. Mossalayi、Pascal Sonnet、Gérard Déléris、Jean Guillon

  DOI：10.3109/14756366.2010.548326

  日期：2011.10.1

  A novel series of isoindolo[2,1-a]quinoxaline and indolo[1,2-a]quinoxaline derivatives was synthesized and evaluated in vitro against various human cancer cell lines for antiproliferative activity. These new compounds displayed activity against leukemia and breast cancer cell lines in the 3- to 18-mu M concentration range.
• [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.