5,6,7-trimethoxy-2-methyl-1H-indole | 1416868-50-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5,6,7-trimethoxy-2-methyl-1H-indole
• CAS: 1416868-50-2
• 化学式: C₁₂H₁₅NO₃
• 分子量: 221.256
• InChiKey: HBMFTBOBMKEZHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  43.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5,6,7-trimethoxy-2-methyl-1H-indole 在 palladium 10% on activated carbon 、 乙基溴化镁 、 甲酸铵 、 zinc(II) chloride 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 生成 (3-hydroxy-4-methoxyphenyl)-(5,6,7-trimethoxy-2-methyl-1H-indol-3-yl)methanone
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of N-Methyl-5,6,7-trimethoxylindoles as Novel Antimitotic and Vascular Disrupting Agents

  摘要：

  Several new series of 5,6,7-trimethoxyindole derivatives were synthesized and their structure-activity relationships (SARs) were studied. Some of these compounds exhibited strong antiproliferative activities in the submicromolar range. N-Methyl-5,6,7-trimethoxylindoles 21 and 31 displayed the highest antiproliferative activities, with IC50 values ranging from 22 to 125 nM in four human cancer cell lines and activated human umbilical vein endothelial cells (HUVECs). In addition to vascular disrupting activity verified by in vitro assays, compounds 21 and 31 displayed much higher selectivity for activated HUVECs versus quiescent HUVECs than those of colchicine and combretastatinA-4. The polymerization of cancer cell tubulin was inhibited and the cell cycle was arrested in the G2/M phase after treatment with 21 and 31. It was showed that 21 disrupted tumor vasculature by use of in vivo assay. Our results suggest that these two new compounds we synthesized may become the promising leads for the development of vascular disrupting agents.

  DOI：

  10.1021/jm3014663

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。
• Thieno[2,3-e]indole derivatives as new antitumor agents
  申请人：NERVIANO MEDICAL SCIENCES S.R.L.

  公开号：US10266547B2

  公开（公告）日：2019-04-23

  The present invention relates to a novel class of alkylating agents comprising a thieno[2,3-e]indole moiety tethered to a DNA-binding moiety, which have cytotoxic activity and are useful in treating diseases such as cancer, cellular proliferation disorders and viral infections. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising them and methods of treating diseases utilizing such compounds or the pharmaceutical composition containing them. The invention also relates to the use of this novel class of alkylating agents in the preparation of conjugates.

  本发明涉及一类新型烷化剂，该类烷化剂包含一个与 DNA 结合基相连的噻吩并[2,3-e]吲哚分子，具有细胞毒性活性，可用于治疗癌症、细胞增殖障碍和病毒感染等疾病。本发明还提供了制备这些化合物的方法、含有这些化合物的药物组合物以及利用这些化合物或含有这些化合物的药物组合物治疗疾病的方法。本发明还涉及这类新型烷化剂在制备共轭物中的用途。
• NEW ALKYLATING AGENTS
  申请人：Nerviano Medical Sciences S.r.l.

  公开号：EP2836494B1

  公开（公告）日：2019-08-21
• THIENO[2,3-E]INDOLE DERIVATIVES AS NEW ANTITUMOR AGENTS
  申请人：Nerviano Medical Sciences S.r.l.

  公开号：EP3049420B1

  公开（公告）日：2019-05-15
• THIENO-INDOLE MOIETIES AND METHODS OF TREATING USING THE SAME
  申请人：NERVIANO MEDICAL SCIENCES S.R.L.

  公开号：US20170071907A1

  公开（公告）日：2017-03-16

  The present invention relates to a novel class of alkylating agents comprising a thieno-indole moiety linked to a DNA-binding moiety, which have cytotoxic activity and are useful in treating diseases such as cancer, cellular proliferation disorders and viral infections. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising them and methods of treating diseases utilizing such compounds or the pharmaceutical composition containing them. The invention also relates to the use of this novel class of alkylating agents in the preparation of conjugates.