13-(4-fluorobenzyl)coptisine chloride

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 原小檗碱生物碱及其衍生物
• 英文名称: 13-(4-fluorobenzyl)coptisine chloride
• 英文别名: 13-(4-fluorobenzyl)coptisine；24-[(4-Fluorophenyl)methyl]-5,7,17,19-tetraoxa-13-azoniahexacyclo[11.11.0.02,10.04,8.015,23.016,20]tetracosa-1(13),2,4(8),9,14,16(20),21,23-octaene;chloride；24-[(4-fluorophenyl)methyl]-5,7,17,19-tetraoxa-13-azoniahexacyclo[11.11.0.02,10.04,8.015,23.016,20]tetracosa-1(13),2,4(8),9,14,16(20),21,23-octaene;chloride
• 化学式: C₂₆H₁₉FNO₄*Cl
• 分子量: 463.893
• InChiKey: BLSPUHMCENTOIU-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.54
• 重原子数：
  33
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  40.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  13-(4-fluorobenzyl)coptisine chloride 在 甲醇 、 sodium tetrahydroborate 、 potassium carbonate 、 sodium hydroxide 作用下， 反应 2.0h， 以70.2%的产率得到13-(4-fluorobenzyl)dihydrocoptisine
  参考文献：
  名称：

  黄连碱类生物碱衍生物及其抗溃疡性结肠炎 的用途

  摘要：

  本发明涉及以黄连碱季铵盐为原料经衍生化反应获得的新的13‑取代黄连碱季铵盐类衍生物、13‑取代二氢黄连碱类生物碱衍生物和13‑取代四氢黄连碱类生物碱衍生物、其制备方法及其药物用途；其药物用途特征是：所述黄连碱类生物碱衍生物或其生理上可接受的盐在分子水平的活性测试实验中分别显示出一定的或较显著的xbp1启动子转录激活效应，是在治疗溃疡性结肠炎方面具有较高药用价值的化合物。

  公开号：

  CN104211709B
• 作为产物：
  描述：

  氯化黄连碱 在 sodium iodide 、 sodium hydroxide 作用下， 以 乙腈 为溶剂， 反应 1.0h， 生成 13-(4-fluorobenzyl)coptisine chloride
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of Quaternary Coptisine Derivatives as Potential Anti-ulcerative Colitis Agents

  摘要：

  Thirty quaternary coptisine derivatives from a synthesized library were found to activate the in vitro transcription of x-box-binding protein 1 (XBP1). Among these, the dihydrocoptisines were demonstrated by in vitro XBP1 transcriptional activity assays and animal experiments to be much more active anti-ulcerative colitis (UC) agents than quaternary coptisines, tetrahydrocoptisines, and the positive control. Unsubstituted dihydrocoptisine exhibited more significant anti-UC efficacy than dihydrocoptisines substituted at the C-8 or C-13 position. The EC50 value of dihydrocoptisine for XBP1 transcriptional activation was 2.25 nM. Dihydrocoptisine exhibited a significant dose effect relationship, as indicated by biomarkers in in vitro and in vivo experiments. According to this study, the starting material's reductive states and the substitution patterns of the dihydrocoptisines were determined to be the critical parameters for modulating their anti-UC efficacy, and the dihydrocoptisine skeleton was designated as the key pharmacophore. The synthesized dihydrocoptisine is a promising lead for developing anti-UC drugs.

  DOI：

  10.1021/acs.jmedchem.5b00964

文献信息

• 黄连碱类生物碱衍生物及其抗溃疡性结肠炎 的用途
  申请人：中国医学科学院药物研究所

  公开号：CN104211709B

  公开（公告）日：2018-09-25

  本发明涉及以黄连碱季铵盐为原料经衍生化反应获得的新的13‑取代黄连碱季铵盐类衍生物、13‑取代二氢黄连碱类生物碱衍生物和13‑取代四氢黄连碱类生物碱衍生物、其制备方法及其药物用途；其药物用途特征是：所述黄连碱类生物碱衍生物或其生理上可接受的盐在分子水平的活性测试实验中分别显示出一定的或较显著的xbp1启动子转录激活效应，是在治疗溃疡性结肠炎方面具有较高药用价值的化合物。
• Synthesis and Structure–Activity Relationships of Quaternary Coptisine Derivatives as Potential Anti-ulcerative Colitis Agents
  作者：Zhi-Hui Zhang、Hai-Jing Zhang、An-Jun Deng、Bo Wang、Zhi-Hong Li、Yang Liu、Lian-Qiu Wu、Wen-Jie Wang、Hai-Lin Qin

  DOI：10.1021/acs.jmedchem.5b00964

  日期：2015.9.24

  Thirty quaternary coptisine derivatives from a synthesized library were found to activate the in vitro transcription of x-box-binding protein 1 (XBP1). Among these, the dihydrocoptisines were demonstrated by in vitro XBP1 transcriptional activity assays and animal experiments to be much more active anti-ulcerative colitis (UC) agents than quaternary coptisines, tetrahydrocoptisines, and the positive control. Unsubstituted dihydrocoptisine exhibited more significant anti-UC efficacy than dihydrocoptisines substituted at the C-8 or C-13 position. The EC50 value of dihydrocoptisine for XBP1 transcriptional activation was 2.25 nM. Dihydrocoptisine exhibited a significant dose effect relationship, as indicated by biomarkers in in vitro and in vivo experiments. According to this study, the starting material's reductive states and the substitution patterns of the dihydrocoptisines were determined to be the critical parameters for modulating their anti-UC efficacy, and the dihydrocoptisine skeleton was designated as the key pharmacophore. The synthesized dihydrocoptisine is a promising lead for developing anti-UC drugs.