12-N-(3,4,5-trimethoxybenzyl)sophoridine butyric acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 12-N-(3,4,5-trimethoxybenzyl)sophoridine butyric acid
• 英文别名: 12-N-(3,4,5-trimethoxybenzyl)sophoridinic acid；4-[(5R,6R,9R,13S)-7-[(3,4,5-trimethoxyphenyl)methyl]-1,7-diazatricyclo[7.3.1.05,13]tridecan-6-yl]butanoic acid
• 化学式: C₂₅H₃₈N₂O₅
• 分子量: 446.587
• InChiKey: PYARTGAUUQLDEB-FIXDAVPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  71.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  槐定碱 在 盐酸 、 三乙胺 作用下， 以 水 、 1,2-二氯乙烷 为溶剂， 反应 13.0h， 生成 12-N-(3,4,5-trimethoxybenzyl)sophoridine butyric acid
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Sophoridinol Derivatives as a Novel Family of Potential Anticancer Agents

  摘要：

  New N-substituted sophoridinic acid/ester and sophoridinol derivatives were synthesized and evaluated for their cytotoxic activity in human HepG2 hepatoma cells from the lead sophoridine (1). Among the newly synthesized compounds, sophoridinol 7i displayed a potential antiproliferative activity with an IC50 of 3.1 mu M. Importantly, it exerted an almost equipotent effect against both wild MCF-7 and adriamycin (AMD)-resistant MCF-7 (MCF-7/AMD) breast carcinoma cell lines. Its mode of action was to arrest the cell cycle at the G0/G1 phase, consistent with that of the parent 1. In addition, compound 7i also showed a reasonable ClogP value and favorable pharmacokinetic property with an area under the concentrationtime curve (AUC) of 10.3 mu M.h in rats, indicating an ideal druggable characteristic. We consider sophoridinol derivatives to be a novel family of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.

  DOI：

  10.1021/ml500289h

文献信息

• Synthesis and Biological Evaluation of Sophoridinol Derivatives as a Novel Family of Potential Anticancer Agents
  作者：Chongwen Bi、Caixia Zhang、Yinghong Li、Sheng Tang、Shenggang Wang、Rongguang Shao、Haigen Fu、Feng Su、Danqing Song

  DOI：10.1021/ml500289h

  日期：2014.11.13

  New N-substituted sophoridinic acid/ester and sophoridinol derivatives were synthesized and evaluated for their cytotoxic activity in human HepG2 hepatoma cells from the lead sophoridine (1). Among the newly synthesized compounds, sophoridinol 7i displayed a potential antiproliferative activity with an IC50 of 3.1 mu M. Importantly, it exerted an almost equipotent effect against both wild MCF-7 and adriamycin (AMD)-resistant MCF-7 (MCF-7/AMD) breast carcinoma cell lines. Its mode of action was to arrest the cell cycle at the G0/G1 phase, consistent with that of the parent 1. In addition, compound 7i also showed a reasonable ClogP value and favorable pharmacokinetic property with an area under the concentrationtime curve (AUC) of 10.3 mu M.h in rats, indicating an ideal druggable characteristic. We consider sophoridinol derivatives to be a novel family of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.