2-(3,4-dimethoxyphenyl)-3-methoxy-4H-chromen-4-one | 78933-15-0

• 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: 2-(3,4-dimethoxyphenyl)-3-methoxy-4H-chromen-4-one
• 英文别名: 3-O-methyl-3',4'-dimethoxyflavonol；3,3',4'-Trimethoxyflavone；2-(3,4-dimethoxy-phenyl)-3-methoxy-chromen-4-one；2-(3,4-Dimethoxy-phenyl)-3-methoxy-chromen-4-on；2-(3,4-dimethoxyphenyl)-3-methoxychromen-4-one
• CAS: 78933-15-0
• 化学式: C₁₈H₁₆O₅
• 分子量: 312.322
• InChiKey: BSKMLHOVEORMSF-UHFFFAOYSA-N

物化性质

• 熔点：
  165-167 °C(Solv: ethanol (64-17-5))
• 沸点：
  466.0±45.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (2E)-3-(3,4-二甲氧基苯基)-1-(2-羟基苯基)-2-丙烯-1-酮 在 双氧水 、 potassium carbonate 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.17h， 生成 2-(3,4-dimethoxyphenyl)-3-methoxy-4H-chromen-4-one
  参考文献：
  名称：

  一类新型黄酮醇类抗前列腺癌药物：细胞模型的设计、合成和评估

  摘要：

  类黄酮是一大类多酚化合物，广泛分布于食用植物中，具有多种生物活性。黄酮醇是类黄酮的一个主要子类，在 C-3 处具有羟基。某些天然黄酮醇，例如槲皮素和非瑟酮，已通过体外细胞和体内动物实验证明是潜在的抗前列腺癌药物。然而，黄酮醇作为候选药物的致命弱点是其效力适中且药代动力学特征较差。本研究旨在探讨黄酮醇中 3-OH 的替代效应对雄激素敏感和雄激素不敏感的人前列腺癌细胞系的体外抗增殖效力。我们通过醇醛缩合合成了第一个铅黄酮醇（3',4'-二甲氧基黄酮醇）、八种3- O-烷基-3',4'-二甲氧基黄酮醇和六种3- O-氨基烷基-3',4'-二甲氧基黄酮醇以及阿尔加-弗林-小山田 (AFO) 反应。 WST-1 细胞增殖测定表明 (i) 所有合成的 3- O-烷基-3',4'-二甲氧基黄酮醇和 3- O-氨基烷基-3',4'-二甲氧基黄酮醇都比母体 3' 更有效， 4′-二甲氧基黄酮醇和天然黄酮醇槲皮素抑制前列腺癌细胞增殖；

  DOI：

  10.1016/j.bmcl.2016.07.050

文献信息

• Structure-activity relationship and pharmacokinetic studies of 3-O-substitutedflavonols as anti-prostate cancer agents
  作者：Xiang Li、Changde Zhang、Shanchun Guo、Pravien Rajaram、Maizie Lee、Guanglin Chen、Ryan Fong、Aaron Gonzalez、Qiang Zhang、Shilong Zheng、Guangdi Wang、Qiao-Hong Chen

  DOI：10.1016/j.ejmech.2018.08.047

  日期：2018.9

  3′,4′,7-trimethoxyflavonol through a 3- to 5-carbon linker can substantially improve the in vitro antiproliferative potency in three human prostate cancer cell models, but not in two non-neoplastic human epithelial cell models (MCF 10A and PWR-1E). 1-Methylpiperazine, pyrrolidine, and dibutylamine are optimal terminal amine groups that, in combination with a 3- to 5-carbon linker, are notably beneficial

  合成了38个3- O-取代-3'，4'-二甲氧基黄酮醇和25个3 - O-取代-3'，4'，7-三甲氧基黄酮醇，用于系统研究3-的结构-活性关系。在三种人类前列腺癌细胞模型中，O-取代的3'，4'-二甲氧基黄酮醇。我们的发现表明，通过3至5个碳原子的连接基将适当的氨基掺入3'，4'-二甲氧基黄酮醇和3'，4'，7-三甲氧基黄酮醇的3-OH可以显着改善体外在三种人类前列腺癌细胞模型中具有抗增殖能力，但在两种非肿瘤性人类上皮细胞模型（MCF 10A和PWR-1E）中却没有。1-甲基哌嗪，吡咯烷和二丁胺是最佳的末端胺基，与3至5个碳的连接基结合使用，对3- O-取代的3'，4'-二甲氧基黄酮醇的抗增殖能力特别有益。值得注意的是3- O-（4-甲基哌嗪-1-基）丙基-3'，4'，7-三甲氧基黄酮醇（76）诱导PC-3细胞死亡的方式与3- O-吡咯烷基戊基- 3'，4'，7-三甲氧基黄酮醇（81）即使它们属于3-
• A Structure Activity Relationship Study of 3,4’-Dimethoxyflavone for ArlRS Inhibition in Staphylococcus aureus
  作者：Alexander Weig、Patrick O'Connor、Jakub M. Kwiecinski、Orry Marciano、Angelica Nunag、Andrew Guitierrez、Roberta Melander、Alexander Horswill、Christian Melander

  DOI：10.1039/d3ob00123g

  日期：——

  Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are difficult to treat due to their resistance to many -lactam antibiotics, and their highly coordinated excretion of virulence factors. One way in...

  耐甲氧西林金黄色葡萄球菌（MRSA）引起的感染很难治疗，因为它们对许多  内酰胺类抗生素都有耐药性，而且毒性因子的排泄高度协调。其中一种方法是...
• Synthesis and biological evaluation of flavones and benzoflavones as inhibitors of BCRP/ABCG2
  作者：Kapil Juvale、Katja Stefan、Michael Wiese

  DOI：10.1016/j.ejmech.2013.06.035

  日期：2013.9

  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.
• Dhoubhadel, S. P.; Tuladhar, Sudersan M.; Tuladhar, Sarbajna M., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1981, vol. 20, # 6, p. 511 - 512
  作者：Dhoubhadel, S. P.、Tuladhar, Sudersan M.、Tuladhar, Sarbajna M.、Wagley, Pradyumna P.

  DOI：——

  日期：——
• Hattori, Bulletin of the Chemical Society of Japan, 1927, vol. 2, p. 175
  作者：Hattori

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