N-demethylsinomenine | 240131-71-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: N-demethylsinomenine
• 英文别名: 17-Demethylsinomenine；(1R,9S,10S)-3-hydroxy-4,12-dimethoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5,11-tetraen-13-one
• CAS: 240131-71-9
• 化学式: C₁₈H₂₁NO₄
• 分子量: 315.369
• InChiKey: BJJRDCBDIOEIKD-FTLABTOESA-N

物化性质

• 熔点：
  222-223 °C(Solv: chloroform (67-66-3))
• 沸点：
  519.7±50.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 储存条件：
  储存温度应控制在2-8°C，需保持干燥并密封保存。

反应信息

• 作为反应物：
  描述：

  N-demethylsinomenine 在 manganese(IV) oxide 作用下， 以 甲醇 为溶剂， 反应 72.0h， 生成 (R)-17-Demethyldisinomenine
  参考文献：
  名称：

  青藤碱类似物独特的立体二聚体作为NO生成的潜在抑制剂的合成和生物学评估

  摘要：

  抑制过量NO的产生已被认为是治疗类风湿关节炎（RA）的潜在手段。为了发现更多有效的抑制剂并探索初步的结构活性关系，设计并合成了一系列独特的青藤碱类似物立体异构体。分别使用LPS激活的鼠巨噬细胞RAW264.7测定法和MTT方法评估了它们对NO产生的抑制活性和细胞毒性。在这些化合物中，1A，2，图2a，图2b，和4显示出对NO产生有效的抑制活性无明显的细胞毒性。此外，2，图2a和2b中显着抑制iNOS的mRNA表达。有趣的是，（S）-二聚体显示出比（R）-二聚体更好的生物活性。这些化合物可以作为RA治疗的新型治疗药物开发中的主要候选药物。

  DOI：

  10.1016/j.bmc.2011.04.006
• 作为产物：
  描述：

  青藤碱 在 ferrous(II) sulfate heptahydrate 、 双氧水 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 N-demethylsinomenine
  参考文献：
  名称：

  青藤碱类似物独特的立体二聚体作为NO生成的潜在抑制剂的合成和生物学评估

  摘要：

  抑制过量NO的产生已被认为是治疗类风湿关节炎（RA）的潜在手段。为了发现更多有效的抑制剂并探索初步的结构活性关系，设计并合成了一系列独特的青藤碱类似物立体异构体。分别使用LPS激活的鼠巨噬细胞RAW264.7测定法和MTT方法评估了它们对NO产生的抑制活性和细胞毒性。在这些化合物中，1A，2，图2a，图2b，和4显示出对NO产生有效的抑制活性无明显的细胞毒性。此外，2，图2a和2b中显着抑制iNOS的mRNA表达。有趣的是，（S）-二聚体显示出比（R）-二聚体更好的生物活性。这些化合物可以作为RA治疗的新型治疗药物开发中的主要候选药物。

  DOI：

  10.1016/j.bmc.2011.04.006

文献信息

• Access to a Structurally Complex Compound Collection via Ring Distortion of the Alkaloid Sinomenine
  作者：Alfredo Garcia、Bryon S. Drown、Paul J. Hergenrother

  DOI：10.1021/acs.orglett.6b02333

  日期：2016.10.7

  Many compound collections used in high-throughput screening are composed of members whose structural complexity is considerably lower than that of natural products. We previously reported a strategy for the synthesis of complex and diverse small molecules from natural products using ring-distortion reactions, called complexity-to-diversity (CtD), and herein, CtD is applied in the synthesis of 16 diverse

  许多用于高通量筛选的化合物集合由结构复杂性远低于天然产物的成员组成。我们之前报道了一种利用环畸变反应从天然产物中合成复杂多样的小分子的策略，称为复杂性到多样性（CtD），在这里，CtD被应用于合成16种不同的支架和65种总化合物来自生物碱天然产物青藤碱。化学信息分析表明这些化合物具有复杂的环系和明显的三维性。
• Metabolic mechanism and anti-inflammation effects of sinomenine and its major metabolites N-demethylsinomenine and sinomenine-N-oxide
  作者：Qiang Li、Wenbin Zhou、Yuyan Wang、Fang Kou、Chunming Lyu、Hai Wei

  DOI：10.1016/j.lfs.2020.118433

  日期：2020.11

  Aims: Sinomenine (SIN) is clinically used as an anti-rheumatic drug. However, the metabolic and pharmacological mechanisms of SIN combined with its metabolites are unclear. This study aims to explore the cyclic metabolic mechanism of SIN, the anti-inflammation effects of SIN and its major metabolites (N-demethylsinomenine (DS) and sinomenine-N-oxide (SNO)), and the oxidation property of SNO.Materials and methods: SIN was administrated to rats via gavage. Qishe pills (a SIN-containing drug) were orally administrated to humans. The bio-samples were collected to identify SIN'S metabolites. Enzymatic and nonenzymatic incubations were used to reveal SIN'S metabolic mechanism. Impacts of SIN, SNO and DS on the inflammation-related cytokine's levels and nuclear translocation of NF-kappa B were evaluated in LPS-induced Raw264.7 cells. ROS induced by SNO (10 mu M) was also assessed.Key findings: CYP3A4 and ROS predominantly mediated the formation of SNO, and CYP3A4 and CYP2C19 primarily mediated the formation of DS. Noteworthily, SNO underwent N-oxide reduction both enzymatically, by xanthine oxidase (XOD), and non-enzymatically, by ferrous ion and heme moiety. The levels of IL-6 and TNF-alpha and nuclear translocation of NF-kappa B were ameliorated after pretreatment of SIN in LPS-induced Raw264.7 cells, while limited attenuations were observed after pretreatment of DS (SNO) even at 200 mu M. In contrast, SNO induced ROS production.Significance: This study elucidated that SIN underwent both enzymatic and non-enzymatic cyclic metabolism and worked as the predominant anti-inflammation compound, while SNO induced ROS production, suggesting more studies of SIN combined with SNO and DS are necessary in case of DDI and potential toxicities.