5,6-Diacetoxy-7-benzyloxyflavon | 67047-06-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 5,6-Diacetoxy-7-benzyloxyflavon
• 英文别名: 7-benzyloxy-5,6-diacetoxyflavone；5,6-diacetoxy-7-benzyloxy-flavone；7-(benzyloxy)-4-oxo-2-phenyl-4H-1-benzopyran-5,6-diyl diacetate；5,6-diacetoxy-7-(benzoxy)flavone；(5-Acetyloxy-4-oxo-2-phenyl-7-phenylmethoxychromen-6-yl) acetate
• CAS: 67047-06-7
• 化学式: C₂₆H₂₀O₇
• 分子量: 444.441
• InChiKey: JQUCDFUJMVWQOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5,6-Diacetoxy-7-benzyloxyflavon 在 palladium on activated charcoal 氢气 作用下， 以 丙酮 为溶剂， 生成 黄芩苷
  参考文献：
  名称：

  Mezey-Vandor, Gabriella; Farkas, Lorand; Kanzel, Ida, Chemische Berichte, 1980, vol. 113, # 5, p. 1945 - 1949

  摘要：

  DOI：
• 作为产物：
  描述：

  黄芩素 在 sodium acetate 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 生成 5,6-Diacetoxy-7-benzyloxyflavon
  参考文献：
  名称：

  从 Oroxylum indium 的种子中分离出的天然黄酮苷、oroxins C 和 D 的简明合成和抗糖尿病活性

  摘要：

  从 Oroxylum indicum 的种子中分离出的天然黄酮苷类化合物 C (1) 和 D (2) 的首次简洁合成是通过收敛策略有效实现的。这 ...

  DOI：

  10.1177/1747519820927966

文献信息

• [EN] COMPOUNDS AND METHODS TO INCREASE ANTI-P-GLYCOPROTEIN ACTIVITY OF BAICALEIN BY ALKYLATION ON THE A RING<br/>[FR] COMPOSES ET METHODES DESTINEES A AUGMENTER L'ACTIVITE ANTI-GLYCOPROTEINE P PAR ALKYLATION SUR LE NOYAU A
  申请人：UNIV YALE

  公开号：WO2005075449A1

  公开（公告）日：2005-08-18

  The present invention is directed to analogs of baicalein according to formula (I): where R5 is H, (CI-C12)alkyl, (C2-C13)acyl, or an optionally substituted phenyl or benzyl group, an acyl group, a C1-C20 alkyl or ether group, a phosphate, diphosphate, triphosphate or phosphodiester group; R6 and R7 are each independently H, (C1-C12)alkyl, (C2-C13)acyl, or an optionally substituted phenyl or benzyl or together form a -OCR1R20- group wherein each of R1 and R2 is independently H, a C1-C3 alkyl group or an optionally substituted phenyl or benzyl group; and R8 is H, OH, an O-acyl group, a C1,-C4 alkyl or alkoxy group, F, Cl, Br or I, or a pharmaceutically acceptable salt thereof, which exhibit anti-P-glycoprotein activity and methods of enhancing the bioavailability of active compounds, especially orally administered compounds, by inhibition of P-glycoprotein 170 (P-gp 170) and/or CYP450 enzyme, especially CYP450 3A4 enzyme. Pharmaceutical compositions based upon these novel derivatives according to the present invention are also described herein.

  本发明涉及根据式(I)的黄芩素类似物：其中R5为H，(C1-C12)烷基，(C2-C13)酰基，或者一个可选择取代的苯基或苄基团，酰基，C1-C20烷基或醚基，磷酸酯，二磷酸酯，三磷酸酯或磷酸二酯基团；R6和R7各自独立地为H，(C1-C12)烷基，(C2-C13)酰基，或者一个可选择取代的苯基或苄基，或者一起形成一个-OCR1R20-基团，其中R1和R2中的每一个独立地为H，C1-C3烷基或可选择取代的苯基或苄基团；以及R8为H，OH，一个O-酰基团，一个C1-C4烷基或烷氧基团，F，Cl，Br或I，或其药学上可接受的盐，具有抗P-糖蛋白活性，并通过抑制P-糖蛋白170 (P-gp 170)和/或CYP450酶，特别是CYP450 3A4酶，来增强活性化合物的生物利用度的方法。根据本发明的这些新颖衍生物基础上的药物组合物也在此描述。
• Novel synthetic baicalein derivatives caused apoptosis and activated AMP-activated protein kinase in human tumor cells
  作者：Derong Ding、Baozi Zhang、Tao Meng、Ying Ma、Xin Wang、Hongli Peng、Jingkang Shen

  DOI：10.1039/c1ob06094e

  日期：——

  Studies on the anti-proliferative activities of novel baicalein derivatives demonstrated that compounds 8 and 9 were able to activate AMPK by enhancing the levels of phosphorylated AMPKα, and showed more potent anti-proliferative effects than baicalein and AICAR in A431, SK-OV-3, DU 145 and HeLa cells, suggesting an alternative therapeutic approach for benzyl baicalein in cancer therapy.

  对新型黄岑酚衍生物的抗增殖活性研究表明，化合物8和9通过增强磷酸化AMPKα的水平激活AMPK，并且在A431、SK-OV-3、DU 145和HeLa细胞中表现出比黄岑酚和AICAR更强的抗增殖效果，提示了苄基黄岑酚在癌症治疗中的一种替代疗法。
• Synthesis of Ring A-Modified Baicalein Derivatives
  作者：Jun-Fei Wang、Ning Ding、Wei Zhang、Peng Wang、Ying-Xia Li

  DOI：10.1002/hlca.201100162

  日期：2011.12

  Baicalein, an important active constituent of the traditional Chinese herb Scutellaria baicalensis, exhibited antitumor activity and inhibitory activity against P‐gp 170. The syntheses of 25 baicalein derivatives, 2–26 (Table), are described here (Scheme 1). These compounds were systematically modified with O‐alkylation and O‐acylation at HOC(5), HOC(6), and HOC(7), singly or in combination, on

  黄ical素是传统中草药黄cut的重要活性成分，具有抗P-gp 170的抗肿瘤活性和抑制活性。这里描述了25种黄ical素衍生物2 – 26的合成（表1）（方案1）。这些化合物进行了系统的修饰ö烷基化和ö酰化在HO  C（5），HO  C（6），和HO  C（7），单独或组合，在环甲为了评价这样的修改对他们的抑制活性对耐多药的肿瘤细胞系和P-gp的作用的黄芩素170在110的高选择性，高效的烷基化全乙酰化的黄芩素C（7）是关键的区别HO  C（6）和HO 黄芩素的C（7）。
• 一种千层纸素的合成方法
  申请人：北京恩成康泰生物科技有限公司

  公开号：CN111100103A

  公开（公告）日：2020-05-05

  本发明涉及一种千层纸素的合成方法。本发明所述的方法是以5，6，7‑三羟基黄酮在吡啶中与醋酸酐室温下发生乙酰化反应；得到的乙酰化物在无机碱存在下与溴苄或氯苄反应，生成物在碱水下进行水解反应；接着在无机碱存在下与碘甲烷反应，最后在浓硫酸存在下脱苄基得到目标产物千层纸素。本发明所提供的合成千层纸素的方法具有操作简单易行、产品纯度高、反应收率高等优点，较之于现行方法更易于工业化生产。
• Increased Anti-P-glycoprotein Activity of Baicalein by Alkylation on the A Ring
  作者：Yashang Lee、Hosup Yeo、Shwu-Huey Liu、Zaoli Jiang、Ruben M. Savizky、David J. Austin、Yung-chi Cheng

  DOI：10.1021/jm049949c

  日期：2004.10.1

  The aqueous extract of Scutellariae baicalensis Georgi has inhibitory activity against P-gp 170, a multiple drug resistant gene product. Baicalein, one of the major flavones, was found to be responsible for this activity. The hydroxyl groups of the A ring of baicalein were systematically alkylated in order to assess the effect of such modifications on the activity against P-gp 170. The impact of the baicalein modifications on activity against the growth of a human nasopharyngeal. cancer cell line KB and its P-gp 170 overexpressing cell line KB/MDR were also examined. The results indicate that alkylation of R5 of baicalein does not have a major impact on the interaction with P-gp 170, whereas alkylation of R6 or R7 alone or both, could enhance the interaction of baicalein with P-gp 170 as well as the amount of intracellular accumulation of vinblastine, a surrogate marker for the activity of P-gp 170 pump of KB/MDR cells. In this case, the optimal linear alkyl functionality is a propyl side chain. These modifications could also alter the activity of compounds inhibiting cell growth. Among the different compounds synthesized, the most potent molecule against P-gp 170 is 5-methoxy-6,7-dipropyloxyflavone (23). Its inhibitory activity against P-gp 170 is approximately 40 times better, based on EC50 (concentration of the compound enhancing 50% of the intracellular vinblastine accumulation in the KB/MDR cells) and 3 times higher, based on A(max) (the intracellular vinblastine accumulation of the KB/MDR cells caused by the compound) as compared to baicalein. Compound 23 is also a more selective inhibitor than baicalein against P-gp 170, because its cytotoxicity is less than that observed for baicalein. The growth inhibitory IC50 of compound 23 against KB and KB/MDR cells are about the same, suggesting that compound 23 is unlikely to be a substrate of P-gp 170 pump. Acetylation of R6, R7 or both could also decrease EC50 and increase A(max). Acetylated compounds are more toxic than baicalein, and their potency against cell growth is compromised by the presence of P-gp 170, suggesting that these compounds are substrates of P-gp 170. Benzylation of R6 or R7 but not both also enhanced anti-P-gp170 activity and potency against cell growth; however, the presence of P-gp 170 in cells did not have an impact on their sensitivity to these molecules, suggesting that the benzylated compounds are inhibitors but not substrates of P-gp 170, and perhaps have a different mechanism of action. In conclusion, the substitutions of R6 and R7 hydroxyl groups by alkoxy groups, acetoxy groups, or benzyloxy groups could yield compounds with different modes of action against P-gp 170 with different mechanisms of action against cell growth.