5,6,7-trimethoxy-1H-indole | 37174-47-3

• 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-1H-indole
• 英文别名: 5,6,7-Trimethoxy-indol；5,6,7-trimethoxyindole；5.6.7-Trimethoxy-indol
• CAS: 37174-47-3
• 化学式: C₁₁H₁₃NO₃
• 分子量: 207.229
• InChiKey: IRNYYMPRGUFZGX-UHFFFAOYSA-N

物化性质

• 熔点：
  82.0-84.3 °C
• 沸点：
  133-134 °C(Press: 0.7 Torr)
• 密度：
  1.191±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 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-1H-indole 在 ammonium acetate 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 28.0h， 生成 2-amino-4-(3,4-difluorophenyl)-6-(5,6,7-trimethoxy-1H-indol-3-yl)nicotinonitrile
  参考文献：
  名称：

  Synthesis and anti-tumor activity of 2-amino-3-cyano-6-(1H-indol-3-yl)-4-phenylpyridine derivatives in vitro

  摘要：

  A series of novel 2-amino-3-cyano-6-(1H-indol-3-yl)-4-phenylpyridine derivatives were synthesized and their cytotoxic activity against A549, H460, HT-29 and SMMC-7721 cell lines was evaluated in vitro. Among them, ten compounds (10, 11, 14, 16, 17, 26, 27, 29, 30 and 31) displayed excellent anti-tumor activity against different cell lines. The most promising compound 27 showed strong anti-tumor activity against A549, H460, HT-29 and SMMC-7721 cell lines with IC50 values of 22, 0.23, 0.65 and 0.77 nM, which were 2.6-, 83-, 1.1 x 10(3)- and 2.0 x 10(3)- fold more active than MX-58151 (IC50 values of 0.058, 0.019, 0.70 and 1.53 mu M), respectively. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.03.055
• 作为产物：
  描述：

  2-nitro-3,4,5-trimethoxybenzaldehyde 在 ammonium acetate 、 铁粉 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 反应 3.5h， 生成 5,6,7-trimethoxy-1H-indole
  参考文献：
  名称：

  Concise syntheses of N-aryl-5,6,7-trimethoxyindoles as antimitotic and vascular disrupting agents: application of the copper-mediated Ullmann-type arylation

  摘要：

  为了模拟 combretastatin A-4 中的 3,4,5-三甲氧基苯基-Z-苯乙烯结构，合成了一系列 N-芳基-5,6,7-三甲氧基吲哚化合物，采用通过相应的 5,6,7-三甲氧基吲哚和芳基卤化物进行的铜催化 Ullmann 型 N-芳基化反应。这些合成的化合物显示出强大的抗增殖活性，为有效的微管聚合抑制剂提供了新的骨架。

  DOI：

  10.1039/c0ob01038c

文献信息

• CBI analogues of the duocarmycins and CC-1065
  申请人：Boger L. Dale

  公开号：US20050026987A1

  公开（公告）日：2005-02-03

  An extensive series of CBI analogues of the duocarmycins and CC-1065 exploring substituent effects within the first indole DNA binding subunit is detailed. In general, substitution at the indole C5 position led to cytotoxic potency enhancements that can be ≧1000-fold providing simplified analogues containing a single DNA binding subunit that are more potent (IC 50 =2-3 pM) than CBI-TMI, duocarmycin SA, or CC-1065. The increases in cytotoxicity correlate well with accompanying increases in the rate and efficiency of DNA alkylation. This effect is more pronounced with the CBI versus DSA or CPI based analogues. Moreover, this effect is largely insensitive to the electronic character of the C5 substituent but is sensitive to the size, rigid length, and shape (sp, sp 2 , sp 3 hybridization) of this substituent consistent with expectation that the impact is due simply to its presence.

  一系列广泛的CBI类似物，包括二聚卡蜜素和CC-1065的类似物，探索了第一个吲哚DNA结合亚基中取代基效应的细节。一般来说，在吲哚C5位置的取代导致细胞毒性增强，可以达到≧1000倍，提供了更强效（IC50=2-3 pM）的含有单个DNA结合亚基的简化类似物，比CBI-TMI、二聚卡蜜素SA或CC-1065更有效。细胞毒性增加与DNA烷基化速率和效率的增加密切相关。与基于DSA或CPI的类似物相比，这种效应在CBI类似物中更为显著。此外，这种效应对于C5取代基的电子性质不太敏感，但对于取代基的大小、刚性长度和形状（sp、sp2、sp3杂化）敏感，这与预期一致，即这种影响仅仅是由于其存在。
• [EN] DUOCARMYCIN ANALOGUES<br/>[FR] ANALOGUES DES DUOCARMYCINES
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2020157662A1

  公开（公告）日：2020-08-06

  The invention relates to 2-methylbenzoxazole compounds of formula I which are analogues of the DNA alkylating subunit of the duocarmycins. Compounds of formula I can be used in the synthesis of DNA alkylating agents and antibody-drug conjugates and related compounds. The 2-methylbenzoxaxole unit of formula I has advantageous properties in combining high cytotoxicity, low lipophilicity, and unusual aqueous stability, all of which are desirable for application as payloads in efficacious antibody-drug conjugates.

  该发明涉及式I的2-甲基苯并噁唑化合物，这些化合物是二氢卡曼霉素的DNA烷基化亚基的类似物。式I的化合物可用于合成DNA烷基化剂、抗体药物结合物和相关化合物。式I的2-甲基苯并噁唑基单元具有有利的特性，包括高细胞毒性、低脂溶性和异常的水稳定性，这些特性对于作为有效的抗体药物结合物中的有效负载是可取的。
• Seco-cyclopropapyrroloindole compounds, antibody-drug conjugates thereof, and methods of making and use
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US10287291B2

  公开（公告）日：2019-05-14

  seco-Cyclopropapyrroloindole compounds of formula (I) where Hal, R1, R2, and R3 are as defined in the application, are potent anti-cancer agents that can be used in antibody-drug conjugates.

  式 (I) 的仲环丙吡咯吲哚化合物 其中 Hal、R1、R2 和 R3 如本申请中所定义，是可用于抗体-药物共轭物的强效抗癌剂。
• 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。
• Hall, Robin J.; Jackson, Anthony H.; Shannon, Patrick V. R., Journal of Chemical Research, Miniprint, 1990, # 10, p. 2501 - 2519
  作者：Hall, Robin J.、Jackson, Anthony H.、Shannon, Patrick V. R.、Oliveira-Campos, Ana M. F.

  DOI：——

  日期：——