N-[(7S)-1,2,3-trimethoxy-9-oxo-10-(diethylamino)-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide | 6962-03-4

• 分子结构分类: 有机化合物 - 碳氢化合物衍生物 - 环庚三烯酮
• 英文名称: N-[(7S)-1,2,3-trimethoxy-9-oxo-10-(diethylamino)-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide
• 英文别名: 10-(diethylamino)colchicine；N-((S)-10-diethylamino-1,2,3-trimethoxy-9-oxo-5,6,7,9-tetrahydro-benzo[a]heptalen-7-yl)-acetamide；N-((S)-10-Diaethylamino-1,2,3-trimethoxy-9-oxo-5,6,7,9-tetrahydro-benzo[a]heptalen-7-yl)-acetamid；(S)-7-Acetylamino-10-diaethylamino-1,2,3-trimethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-on；Colchicine, 10-demethoxy-10-(diethylamino)-；N-[(7S)-10-(diethylamino)-1,2,3-trimethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide
• CAS: 6962-03-4
• 化学式: C₂₅H₃₂N₂O₅
• mdl: MFCD32724338
• 分子量: 440.539
• InChiKey: VBJDWXFOMWSFLB-IBGZPJMESA-N

物化性质

• 沸点：
  715.9±60.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[(7S)-1,2,3-trimethoxy-9-oxo-10-(diethylamino)-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide 在 硫酸 、 水 作用下， 反应 5.0h， 生成
  参考文献：
  名称：

  Synthesis and Antitumour Activity of Novel Colchicine C-10 Derivatives

  摘要：

  一系列新的秋水仙素C-10衍生物（2a-i，3a-h）通过将10-甲氧基替换为NR2和SCH3合成，旨在确定它们的细胞毒活性。这些化合物以良好产率合成，所有新合成化合物的结构根据其IR、1H NMR和元素分析确定。合成的化合物通过MTT assay在体外对四种人癌细胞株进行了抗肿瘤活性测试。发现许多衍生物显示出显著活性，特别是化合物2a和2b展现出比秋水仙素更强的细胞毒活性。

  DOI：

  10.14233/ajchem.2014.16892
• 作为产物：
  描述：

  秋水仙碱 、 二乙胺 以 甲醇 为溶剂， 以75%的产率得到N-[(7S)-1,2,3-trimethoxy-9-oxo-10-(diethylamino)-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide
  参考文献：
  名称：

  Colchicine derivatives with potent anticancer activity and reduced P-glycoprotein induction liability

  摘要：

  已经确定了几种减少P-糖蛋白诱导责任的秋水仙碱衍生物。

  DOI：

  10.1039/c5ob00406c

文献信息

• Schtschukina et al., Zhurnal Obshchei Khimii, 1951, vol. 21, p. 735,738; engl. Ausg. S. 809, 812
  作者：Schtschukina et al.

  DOI：——

  日期：——
• N-Substituted Colchiceinamides
  作者：Jonathan L. Hartwell、M. V. Nadkarni、J. Leiter

  DOI：10.1021/ja01132a511

  日期：1952.6
• Synthesis, antiproliferative and antibacterial evaluation of C-ring modified colchicine analogues
  作者：Adam Huczyński、Jacek Rutkowski、Katarzyna Popiel、Ewa Maj、Joanna Wietrzyk、Joanna Stefańska、Urszula Majcher、Franz Bartl

  DOI：10.1016/j.ejmech.2014.11.037

  日期：2015.1

  A series of 10 amine derivatives of colchicine have been obtained with high yields by modification at C(10)-OCH3 position of C-ring and characterized by spectroscopic methods. In vitro cytotoxicity has been evaluated against four human tumour cell lines (HL-60, HL-60/vinc, LoVo, LoVo/DX), as well as antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE). From among the compounds tested the most active is colchicine derivative 2h with bis(2-methoxyethyl)amine substituent which is active in nanomolar to sub-micromolar concentrations and is several times more cytotoxic than cisplatin and doxorubicin. This compound is also effective against the methicillin-resistant Staphylococci strains. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Synthesis and Antitumour Activity of Novel Colchicine C-10 Derivatives
  作者：Li Hong Shen、Le Zhang、Hai Xian Wang、Xin Wang、Gai Jiao Zhang

  DOI：10.14233/ajchem.2014.16892

  日期：——

  A series of new colchicine C-10 derivatives (2a-i, 3a-h) were synthesized by replacement of the 10-methoxy with NR2 and SCH3 in order to determine their cytotoxic activity. The compounds were synthesized in good yield and the structures of all newly synthesized compounds were established on the basis of their IR, 1H NMR and elemental analysis. The synthesized compounds were tested in vitro antitumor activity against four human cancer cell lines by MTT assay. It was found that many of the derivatives displayed significant activity, particularly, compound 2a and 2b showed more potent cytotoxic activities than colchicine.

  一系列新的秋水仙素C-10衍生物（2a-i，3a-h）通过将10-甲氧基替换为NR2和SCH3合成，旨在确定它们的细胞毒活性。这些化合物以良好产率合成，所有新合成化合物的结构根据其IR、1H NMR和元素分析确定。合成的化合物通过MTT assay在体外对四种人癌细胞株进行了抗肿瘤活性测试。发现许多衍生物显示出显著活性，特别是化合物2a和2b展现出比秋水仙素更强的细胞毒活性。
• Colchicine derivatives with potent anticancer activity and reduced P-glycoprotein induction liability
  作者：Baljinder Singh、Ashok Kumar、Prashant Joshi、Santosh K. Guru、Suresh Kumar、Zahoor A. Wani、Girish Mahajan、Aashiq Hussain、Asif Khurshid Qazi、Ajay Kumar、Sonali S. Bharate、Bishan D. Gupta、Parduman R. Sharma、Abid Hamid、Ajit K. Saxena、Dilip M. Mondhe、Shashi Bhushan、Sandip B. Bharate、Ram A. Vishwakarma

  DOI：10.1039/c5ob00406c

  日期：——

  Colchicine derivatives with reduced P-gp induction liability have been identified.

  已经确定了几种减少P-糖蛋白诱导责任的秋水仙碱衍生物。