3-tert-butyl 5-[12-oxo-12-(N-deacetylcolchicin-7-N-yl)dodecyl] (4S,5R)-2-(4-methoxyphenyl)-4-phenyl-oxazolidine-3,5-dicarboxylate | 1338797-59-3

• 分子结构分类: 有机化合物
• 英文名称: 3-tert-butyl 5-[12-oxo-12-(N-deacetylcolchicin-7-N-yl)dodecyl] (4S,5R)-2-(4-methoxyphenyl)-4-phenyl-oxazolidine-3,5-dicarboxylate
• CAS: 1338797-59-3
• 化学式: C₅₄H₆₈N₂O₁₂
• 分子量: 937.14
• InChiKey: YQGBDUXZZLKCAB-ZVFAZXFOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.38
• 重原子数：
  68.0
• 可旋转键数：
  21.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  157.39
• 氢给体数：
  1.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  3-tert-butyl 5-[12-oxo-12-(N-deacetylcolchicin-7-N-yl)dodecyl] (4S,5R)-2-(4-methoxyphenyl)-4-phenyl-oxazolidine-3,5-dicarboxylate 在 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 反应 2.5h， 以59%的产率得到(2R,3S)-N-(tert-butoxycarbonyl)phenylisoserine 12-oxo-12-(N-deacetylcolchicin-7-N-yl)dodecyl ester
  参考文献：
  名称：

  Synthesis and SAR requirements of adamantane–colchicine conjugates with both microtubule depolymerizing and tubulin clustering activities

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2011.07.040
• 作为产物：
  描述：

  12-羟基十二酸 在 4-二甲氨基吡啶 、 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 72.0h， 生成 3-tert-butyl 5-[12-oxo-12-(N-deacetylcolchicin-7-N-yl)dodecyl] (4S,5R)-2-(4-methoxyphenyl)-4-phenyl-oxazolidine-3,5-dicarboxylate
  参考文献：
  名称：

  Synthesis and SAR requirements of adamantane–colchicine conjugates with both microtubule depolymerizing and tubulin clustering activities

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2011.07.040