10-hydroxyevodiamine | 1355077-92-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 10-hydroxyevodiamine
• 英文别名: 10-hydroxy-14-methyl-8,13,13b,14- tetrahydroindolo[2′,3′:3,4]pyrido[2,1-b]quinazolin-5(7H)-one；hydroxyevodiamine；7-hydroxy-21-methyl-3,13,21-triazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4(9),5,7,15,17,19-heptaen-14-one
• CAS: 1355077-92-7
• 化学式: C₁₉H₁₇N₃O₂
• 分子量: 319.363
• InChiKey: XYSMNZWLVJYABK-UHFFFAOYSA-N

物化性质

• 沸点：
  633.4±55.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  59.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  10-hydroxyevodiamine 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 10-((4-oxo-4-(2-(piperidin-1-yl)ethoxy)butyryl)oxy)evodiamine
  参考文献：
  名称：

  Water-soluble derivatives of evodiamine: Discovery of evodiamine-10-phosphate as an orally active antitumor lead compound

  摘要：

  DOI：

  10.1016/j.ejmech.2021.113544
• 作为产物：
  描述：

  5-甲氧基色胺 在 三溴化硼 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 生成 10-hydroxyevodiamine
  参考文献：
  名称：

  一种10-羟基吴茱萸碱类抗肿瘤化合物及其制 备方法和应用

  摘要：

  本发明涉及一种10‑羟基吴茱萸碱类化合物及其制备方法和在制备抗肿瘤药物中的用途，其结构如式I所示，该类化合物是新发现的具有全新结构的拓扑异构酶抑制剂，大部分化合物表现出广谱的抗肿瘤活性，部分衍生物对测试的三株肿瘤的IC50小于0.001μg/mL，优于现有技术中类似结构活性最好的化合物(10‑羟基吴茱萸碱)。

  公开号：

  CN105418610B

文献信息

• One-Pot Total Synthesis of Evodiamine and Its Analogues through a Continuous Biscyclization Reaction
  作者：Zi-Xuan Wang、Jia-Chen Xiang、Miao Wang、Jin-Tian Ma、Yan-Dong Wu、An-Xin Wu

  DOI：10.1021/acs.orglett.8b02667

  日期：2018.10.19

  The one-pot total synthesis of evodiamine and its analogues is achieved using a three-component reaction. Through continuous biscyclization, various readily available substrates with good functional group tolerance were easily incorporated into biologically active quinazolinocarboline backbones. The use of triethoxymethane as a cosolvent was crucial for this quick and straightforward transformation

  使用三组分反应可实现一锅法合成乙二胺及其类似物。通过连续的双环化，容易将具有良好官能团耐受性的各种容易获得的底物掺入具有生物活性的喹唑啉代咔啉主链中。三乙氧基甲烷作为助溶剂的使用对于这种快速而直接的转化至关重要。
• 一种含有吲哚醌单元的吴茱萸碱前药及其制备方法与应用
  申请人：陕西中医药大学

  公开号：CN113563336B

  公开（公告）日：2022-12-06

  本发明涉及一种含有吲哚醌单元的吴茱萸碱前药及其制备方法与应用。本发明合成了一系列具有吲哚醌单元的强活性的吴茱萸碱衍生物，对非小细胞肺癌(non‑small cell lung cancer,NSCLC)具有较强的抗增殖活性，且具有剂量和时间依赖性。体外实验评估它们的生物活性，表明合成的化合物对肺癌菌株具有较强的抑制活性。通过分子对接分析，预测了配体与靶蛋白活性位点的结合亲和力，与蛋白质相互作用能力较强。
• New Tricks for an Old Natural Product: Discovery of Highly Potent Evodiamine Derivatives as Novel Antitumor Agents by Systemic Structure–Activity Relationship Analysis and Biological Evaluations
  作者：Guoqiang Dong、Shengzheng Wang、Zhenyuan Miao、Jianzhong Yao、Yongqiang Zhang、Zizhao Guo、Wannian Zhang、Chunquan Sheng

  DOI：10.1021/jm300605m

  日期：2012.9.13

  Evodiamine is a quinazolinocarboline alkaloid isolated from the fruits of traditional Chinese herb Evodiae fructus. Previously, we identified N13-substituted evodiamine derivatives as potent topoisomerase I inhibitors by structure-based virtual screening and lead optimization. Herein, a library of novel evodiamine derivatives bearing various substitutions or modified scaffold were synthesized. Among them, a number of evodiamine derivatives showed substantial increase of the antitumor activity, with GI(50) values lower than 3 nM. Moreover, these highly potent compounds can effectively induce the apoptosis of A549 cells. Interestingly, further computational target prediction calculations in combination with biological assays confirmed that the evodiamine derivatives acted by dual inhibition of topoisomerases I and II. Moreover, several hydroxyl derivatives, such as 10-hydroxyl evodiamine (10j) and 3-amino-10-hydroxyl evodiamine (18g), also showed good in vivo antitumor efficacy and low toxicity at the dose of 1 mg/kg or 2 mg/kg. They represent promising candidates for the development of novel antitumor agents.
• Natural Product Evodiamine with Borate Trigger Unit: Discovery of Potent Antitumor Agents against Colon Cancer
  作者：Xinglin Li、Shanchao Wu、Guoqiang Dong、Shuqiang Chen、Zonglin Ma、Dan Liu、Chunquan Sheng

  DOI：10.1021/acsmedchemlett.9b00513

  日期：2020.4.9

  In order to improve the antitumor potency of the natural product evodiamine, novel boron-containing evodiamine derivatives were designed by incorporating boronic acid and boronate as trigger units. Boronate derivative 13a could be triggered by reactive oxygen species (ROS) in the HCT116 colon cancer cell line and showed excellent antitumor activity in vitro and in vivo. It induced apoptosis in HCT116 cancer cells in a dose-dependent manner and cell growth arrest at the G2 phase.
• An A-ring substituted evodiamine derivative with potent anticancer activity against human non-small cell lung cancer cells by targeting heat shock protein 70
  作者：Hye-Young Min、Yijae Lim、Hyukjin Kwon、Hye-Jin Boo、Seung Yeob Hyun、Junhwa Hong、Suckchang Hong、Ho-Young Lee

  DOI：10.1016/j.bcp.2023.115507

  日期：2023.5