6-acetoxy-5,7-dimethoxy-2-phenyl-chromen-4-one | 137527-39-0

• 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: 6-acetoxy-5,7-dimethoxy-2-phenyl-chromen-4-one
• 英文别名: 6-Acetoxy-5,7-dimethoxy-2-phenyl-chromen-4-on；6-acetoxy-5,7-dimethoxyflavone；(5,7-Dimethoxy-4-oxo-2-phenylchromen-6-yl) acetate
• CAS: 137527-39-0
• 化学式: C₁₉H₁₆O₆
• 分子量: 340.332
• InChiKey: HNBSUTNYSYVACY-UHFFFAOYSA-N

物化性质

• 熔点：
  208-210 °C
• 沸点：
  491.6±45.0 °C(Predicted)
• 密度：
  1.284±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  黄芩素 在 吡啶 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 14.0h， 生成 6-acetoxy-5,7-dimethoxy-2-phenyl-chromen-4-one
  参考文献：
  名称：

  Increased Anti-P-glycoprotein Activity of Baicalein by Alkylation on the A Ring

  摘要：

  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.

  DOI：

  10.1021/jm049949c

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。
• Sastri; Seshadri, Proceedings - Indian Academy of Sciences, Section A, 1946, # 23, p. 273,276
  作者：Sastri、Seshadri

  DOI：——

  日期：——
• Compounds and methods to increase anti-p-glycoprotein activity of baicalein by alkylation on the a ring
  申请人：Cheng Yung-chi

  公开号：US20070161605A1

  公开（公告）日：2007-07-12

  The present invention is directed to analogs of baicalein according to formula (I): where R 5 is H, (C 1 -C 12 )alkyl, (C 2 -C 13 )acyl, or an optionally substituted phenyl or benzyl group, an acyl group, a C 1 -C 20 alkyl or ether group, a phosphate, diphosphate, triphosphate or phosphodiester group; R 6 and R 7 are each independently H, (C 1 -C 12 )alkyl, (C 2 -C 13 )acyl, or an optionally substituted phenyl or benzyl or together form a —OCR 1 R 2 O— group wherein each of R 1 and R 2 is independently H, a C 1 -C 3 alkyl group or an optionally substituted phenyl or benzyl group; and R 8 is H, OH, an O-acyl group, a C 1 ,-C 4 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.
• US7875650B2
  申请人：——

  公开号：US7875650B2

  公开（公告）日：2011-01-25
• 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.