12-N-(4-fluorobenzyl)sophoridine butylmethyl ether | 1616292-75-1

• 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-(4-fluorobenzyl)sophoridine butylmethyl ether
• 英文别名: (5R,6R,9R,13S)-7-[(4-fluorophenyl)methyl]-6-(4-methoxybutyl)-1,7-diazatricyclo[7.3.1.05,13]tridecane
• CAS: 1616292-75-1
• 化学式: C₂₃H₃₅FN₂O
• 分子量: 374.542
• InChiKey: MRGISMWDRZRRMZ-ADHNFCLRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  15.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  槐定碱 在 盐酸 、 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 1,2-二氯乙烷 为溶剂， 反应 8.0h， 生成 12-N-(4-fluorobenzyl)sophoridine butylmethyl ether
  参考文献：
  名称：

  Novel N-substituted sophoridinol derivatives as anticancer agents

  摘要：

  Using sophoridine (1) as the lead compound, a series of new N-substituted sophoridinic acid derivatives were designed, synthesized and evaluated for their cytotoxicity. SAR analysis indicated that introduction of a chlorobenzyl on the 12-nitrogen atom of sophoridinol might significantly enhance the anti-proliferative activity. Of the newly synthesized compounds, sophoridinol analogue 9k exhibited a potent effect against six human tumor cell lines (liver, colon, breast, lung, glioma and nasopharyngeal). The mode of action of 9k was to inhibit the DNA topoisomerase I activity, followed by the G0/G1 phase arrest. It also showed a moderate oral bioavailability and good safety in vivo. Therefore, compound 9k has been selected as a novel-scaffold lead for further structural optimizations or as a chemical probe for exploring anticancer pathways of this kinds of compounds. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.04.069

文献信息

• 新型槐定碱类衍生物槐定酸、槐定醇、槐定酯、 槐定醚及其制备方法和用途
  申请人：中国医学科学院医药生物技术研究所

  公开号：CN104250247B

  公开（公告）日：2016-10-12

  本发明涉及新型槐定碱类衍生物槐定酸、槐定醇、槐定酯、槐定醚及其制备方法和用途。本发明第一方面涉及式I的化合物，或其药学可接受的盐或溶剂合物，其中R1选自丁酸、丁酸甲酯或乙酯、丁醇、丁基甲醚或乙醚；以及R2选自氢、苯甲基、苯乙基、4‑吡啶甲基、2‑呋喃甲基、C1‑5直链或支链的烷基、萘甲基、或蒽基甲基，所述苯基任选地被一个或多个选自下列的取代基取代：C1‑2烷氧基、卤素。本发明还涉及式I化合物的制备方法，包含它们的药物组合物，以及它们在制备用于治疗肿瘤或癌症的药物中的应用。
• Novel N-substituted sophoridinol derivatives as anticancer agents
  作者：Chong-Wen Bi、Cai-Xia Zhang、Ying-Hong Li、Sheng Tang、Hong-Bin Deng、Wu-Li Zhao、Zhen Wang、Rong-Guang Shao、Dan-Qing Song

  DOI：10.1016/j.ejmech.2014.04.069

  日期：2014.6

  Using sophoridine (1) as the lead compound, a series of new N-substituted sophoridinic acid derivatives were designed, synthesized and evaluated for their cytotoxicity. SAR analysis indicated that introduction of a chlorobenzyl on the 12-nitrogen atom of sophoridinol might significantly enhance the anti-proliferative activity. Of the newly synthesized compounds, sophoridinol analogue 9k exhibited a potent effect against six human tumor cell lines (liver, colon, breast, lung, glioma and nasopharyngeal). The mode of action of 9k was to inhibit the DNA topoisomerase I activity, followed by the G0/G1 phase arrest. It also showed a moderate oral bioavailability and good safety in vivo. Therefore, compound 9k has been selected as a novel-scaffold lead for further structural optimizations or as a chemical probe for exploring anticancer pathways of this kinds of compounds. (C) 2014 Elsevier Masson SAS. All rights reserved.