1-(chloromethyl)-7,9-dinitro-1,2-dihydro-3H-benzo[e]indole | 885227-26-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-(chloromethyl)-7,9-dinitro-1,2-dihydro-3H-benzo[e]indole
• 英文别名: 1-(chloromethyl)-7,9-dinitro-2,3-dihydro-1H-benzo[e]indole
• CAS: 885227-26-9
• 化学式: C₁₃H₁₀ClN₃O₄
• 分子量: 307.693
• InChiKey: DXWPKAOYLMPNMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(chloromethyl)-9-nitro-1,2-dihydro-3H-benzo[e]indole 在 硫酸 、 potassium nitrate 作用下， 反应 0.25h， 以37%的产率得到1-(chloromethyl)-5,9-dinitro-1,2-dihydro-3H-benzo[e]indole
  参考文献：
  名称：

  WO2006/43839

  摘要：

  公开号：

文献信息

• Nitrobenzindoles and Their use in Cancer Therapy
  申请人：Denny William Alexander

  公开号：US20080119442A1

  公开（公告）日：2008-05-22

  The present invention relates generally to nitro-1,2-dihydro-3H-benzo[e]indoles and related analogues, to their preparation, and to their use as hypoxia-selective drugs and radiosensitizers for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.

  本发明涉及硝基-1,2-二氢-3H-苯并[e]吲哚及其相关类似物，其制备方法以及其作为低氧选择性药物和放射增敏剂在癌症治疗中的使用，可以单独使用或与辐射和/或其他抗癌药物联合使用。
• WO2006/43839
  申请人：——

  公开号：——

  公开（公告）日：——
• US7718688B2
  申请人：——

  公开号：US7718688B2

  公开（公告）日：2010-05-18
• Hypoxia-Activated Prodrugs: Substituent Effects on the Properties of Nitro <i>seco</i>-1,2,9,9a-Tetrahydrocyclopropa[<i>c</i>]benz[<i>e</i>]indol-4-one (nitroCBI) Prodrugs of DNA Minor Groove Alkylating Agents
  作者：Moana Tercel、Graham J. Atwell、Shangjin Yang、Ralph J. Stevenson、K. Jane Botting、Maruta Boyd、Eileen Smith、Robert F. Anderson、William A. Denny、William R. Wilson、Frederik B. Pruijn

  DOI：10.1021/jm901202b

  日期：2009.11.26

  Nitrochloromethylbenzindolines (nitroCBIs) are a new class of hypoxia-activated prodrugs for antitumor therapy. The recently reported prototypes undergo hypoxia-selective metabolism to form potent DNA minor groove alkylating agents and are selectively toxic to some but not all hypoxic tumor cell lines. Here we report a series of 31 analogues that bear an extra electron-withdrawing substituent that serves to raise the one-electron reduction potential of the nitroCBI. We identify a subset of compounds, those with a basic side chain and sulfonamide or carboxamide substituent, that have consistently high hypoxic selectivity. The best of these, with a 7-sulfonamide substituent, displays hypoxic cytotoxicity ratios of 275 and 330 in Skov3 and HT29 human tumor cell lines, respectively. This compound (28) is efficiently and selectively metabolized to the corresponding aminoCBI, is selectively cytotoxic tinder hypoxia in all 11 cell lines examined, and demonstrates activity against hypoxic tumor cells in a human tumor xenograft in vivo.