N-(7-methoxy-7-oxoheptanoyl)-N-deacetylcolchicine | 1338797-78-6

• 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-(7-methoxy-7-oxoheptanoyl)-N-deacetylcolchicine
• 英文别名: methyl 7-oxo-7-[[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]amino]heptanoate
• CAS: 1338797-78-6
• 化学式: C₂₈H₃₅NO₈
• 分子量: 513.588
• InChiKey: CDSQSYBBMYNTFP-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(7-methoxy-7-oxoheptanoyl)-N-deacetylcolchicine 在 水 、 lithium hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 N-(7-hydroxy-7-oxoheptanoyl)-N-deacetylcolchicine
  参考文献：
  名称：

  The discovery of colchicine-SAHA hybrids as a new class of antitumor agents

  摘要：

  A novel class of colchicine-SAHA hybrids were designed and synthesised based on the synergistic antitumor effect of tubulin inhibitors and histone deacetylases (HDAC) inhibitors. To the best of our knowledge, this is the first design of molecules that are dual inhibitors of tubulin and HDAC. Biological evaluations of these compounds included the inhibitory activity of HDAC, in vitro cell cycle analysis in BEL-7402 cells as well as cytotoxicity in five cancer cell lines. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.049
• 作为产物：
  描述：

  秋水仙碱 在 4-二甲氨基吡啶 、 二碳酸二叔丁酯 、 三乙胺 、 O-(benzotriazol-1-yl)-N,N,N,N-tetramethyluroniumhexafluorophosphate 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 25.5h， 生成 N-(7-methoxy-7-oxoheptanoyl)-N-deacetylcolchicine
  参考文献：
  名称：

  The discovery of colchicine-SAHA hybrids as a new class of antitumor agents

  摘要：

  A novel class of colchicine-SAHA hybrids were designed and synthesised based on the synergistic antitumor effect of tubulin inhibitors and histone deacetylases (HDAC) inhibitors. To the best of our knowledge, this is the first design of molecules that are dual inhibitors of tubulin and HDAC. Biological evaluations of these compounds included the inhibitory activity of HDAC, in vitro cell cycle analysis in BEL-7402 cells as well as cytotoxicity in five cancer cell lines. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.049

文献信息

• Synthesis and SAR requirements of adamantane–colchicine conjugates with both microtubule depolymerizing and tubulin clustering activities
  作者：Olga N. Zefirova、Evgeniya V. Nurieva、Dmitrii V. Shishov、Igor I. Baskin、Fabian Fuchs、Heiko Lemcke、Fabian Schröder、Dieter G. Weiss、Nikolay S. Zefirov、Sergei A. Kuznetsov

  DOI：10.1016/j.bmc.2011.07.040

  日期：2011.9

  A series of analogues of conjugate 1, combining an adamantane-based paclitaxel (taxol) mimetic with colchicine was synthesized and tested for cytotoxicity in a cell-based assay with the human lung carcinoma cell line A549. The most active compounds (10 EC50 2 +/- 1.0 nM, 23 EC50 6 +/- 1.4 nM, 26 EC50 5 +/- 1.8 nM, 28 EC50 11 +/- 1.7 nM, 30 EC50 4.8 +/- 0.5 nM) were found to interfere with the microtubule dynamics in an interesting manner. Treatment of the cells with these compounds promoted disassembly of microtubules followed by the formation of stable tubulin clusters. Structure-activity relationships for the analogues of 23 revealed the sensitivity of both cytotoxicity and tubulin clustering ability to the linker length. The presence of adamantane (or another bulky hydrophobic and non-aromatic moiety) in 23 was found to play an important role in the formation of tubulin clusters. Structural requirements for optimal activity have been partially explained by molecular modeling. (C) 2011 Elsevier Ltd. All rights reserved.
• The discovery of colchicine-SAHA hybrids as a new class of antitumor agents
  作者：Xuan Zhang、Jie Zhang、Linjiang Tong、Yu Luo、Mingbo Su、Yi Zang、Jia Li、Wei Lu、Yi Chen

  DOI：10.1016/j.bmc.2013.03.049

  日期：2013.6

  A novel class of colchicine-SAHA hybrids were designed and synthesised based on the synergistic antitumor effect of tubulin inhibitors and histone deacetylases (HDAC) inhibitors. To the best of our knowledge, this is the first design of molecules that are dual inhibitors of tubulin and HDAC. Biological evaluations of these compounds included the inhibitory activity of HDAC, in vitro cell cycle analysis in BEL-7402 cells as well as cytotoxicity in five cancer cell lines. (C) 2013 Elsevier Ltd. All rights reserved.