3-(3,4-dimethoxyphenyl)-1H-benzo[f]chromen-1-one | 136116-18-2

• 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: 3-(3,4-dimethoxyphenyl)-1H-benzo[f]chromen-1-one
• 英文别名: 1H-Naphtho[2,1-b]pyran-1-one, 3-(3,4-dimethoxyphenyl)-；3-(3,4-dimethoxyphenyl)benzo[f]chromen-1-one
• CAS: 136116-18-2
• 化学式: C₂₁H₁₆O₄
• 分子量: 332.356
• InChiKey: HZACSJPHOPKIHC-UHFFFAOYSA-N

物化性质

• 沸点：
  513.8±50.0 °C(Predicted)
• 密度：
  1.271±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(3,4-dimethoxyphenyl)-1H-benzo[f]chromen-1-one 在 氢碘酸 、 乙酸酐 、 溶剂黄146 作用下， 生成 3',4'-Dihydroxy-beta-naphthoflavone
  参考文献：
  名称：

  CCCLXI：色酮组中的合成实验。第四部分1：4-βα-萘并吡喃酮

  摘要：

  DOI：

  10.1039/jr9310002591
• 作为产物：
  描述：

  3,4-dimethoxy-2'-hydroxy-5',6'-benzochalcone 在 碘 作用下， 以 二甲基亚砜 为溶剂， 以77%的产率得到3-(3,4-dimethoxyphenyl)-1H-benzo[f]chromen-1-one
  参考文献：
  名称：

  Synthesis and biological evaluation of flavones and benzoflavones as inhibitors of BCRP/ABCG2

  摘要：

  Multidrug resistance (MDR) often leads to a failure of cancer chemotherapy. Breast Cancer Resistance Protein (BCRP/ABCG2), a member of the superfamily of ATP binding cassette proteins has been found to confer MDR in cancer cells by transporting molecules with amphiphilic character out of the cells using energy from ATP hydrolysis. Inhibiting BCRP can be a solution to overcome MDR. We synthesized a series of flavones, 7,8-benzoflavones and 5,6-benzoflavones with varying substituents at positions 3, 3' and 4' of the (benzo)flavone structure. All synthesized compounds were tested for BCRP inhibition in Hoechst 33342 and pheophorbide A accumulation assays using MDCK cells expressing BCRP. All the compounds were further screened for their P-glycoprotein (P-gp) and Multidrug resistance-associated protein 1 (MRP1) inhibitory activity by calcein AM accumulation assay to check the selectivity towards BCRP. In addition most active compounds were investigated for their cytotoxicity. It was observed that in most cases 7,8-benzoflavones are more potent in comparison to the 5,6-benzoflavones. In general it was found that presence of a 3-OCH3 substituent leads to increase in activity in comparison to presence of OH or no substitution at position 3. Also, it was found that presence of 3',4'-OCH3 on phenyl ring lead to increase in activity as compared to other substituents. Compound 24, a 7,8-benzoflavone derivative was found to be most potent being 50 times selective for BCRP and showing very low cytotoxicity at higher concentrations. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.06.035

文献信息

• 5,6-Benzoflavones as cholesterol esterase inhibitors: synthesis, biological evaluation and docking studies
  作者：Jatinder V. Singh、Anumeet Kaur、Kavita Bhagat、Manish K. Gupta、Manwinder Singh、Harbinder Singh、Preet Mohinder S. Bedi

  DOI：10.1039/c7md00565b

  日期：——

  with an IC50 value of 0.73 nM against cholesterol esterase. To determine the type of inhibition, enzyme kinetic studies were carried out for B-16, which revealed its mixed-type inhibition approach. Moreover, to figure out the key binding interactions of B-16 with the amino acid residues of the enzyme's active site, molecular protein–ligand docking studies were also performed. B-16 completely blocks the

  在继续努力开发有效的胆固醇酯酶（CEase）抑制剂时，通过改变先前报道的7,8-苯并黄酮中与黄酮骨架相连的苯环的位置，合理设计和合成了一系列5,6-苯并黄酮衍生物。使用分光光度测定法检查所有合成的化合物对胆固醇酯酶（CEase）的抑制潜力。在这四十种化合物中，在体外酶促测定中，七种衍生物（B - 10至B - 16）对CEase的抑制率超过90％。化合物B - 16的IC 50表现出最有希望的活性胆固醇酯酶的值为0.73 nM。为了确定抑制的类型，对B - 16进行了酶动力学研究，揭示了其混合类型的抑制方法。此外，为了弄清B - 16与酶活性位点氨基酸残基的关键结合相互作用，还进行了分子蛋白质-配体对接研究。B - 16完全阻断了CEase的催化组装，并阻止了它参与酯的水解机理。B - 16的良好结合构象表明其作为CEase抑制剂的主要作用。总体而言，研究表明，顺式环A相对于环C的羰基的取