3,5-二羟基黄酮 | 6665-69-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 中文名称: 3,5-二羟基黄酮
• 英文名称: 3,5-dihydroxy-2-phenyl-4H-chromen-4-one
• 英文别名: 3,5-Dihydroxyflavone；DHF；3,5-dihydroxy-2-phenyl-chromen-4-one；3,5-Dihydroxy-2-phenyl-chromen-4-on；dihydroxy flavone；3,5-dihydroxy-2-phenylchromen-4-one
• CAS: 6665-69-6
• 化学式: C₁₅H₁₀O₄
• 分子量: 254.242
• InChiKey: QHYWQIVTVQAKQF-UHFFFAOYSA-N

物化性质

• 熔点：
  145-146 °C
• 沸点：
  451.8±45.0 °C(Predicted)
• 密度：
  1.472±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

ADMET

代谢

3,5-二羟基黄酮已知的人类代谢物包括 (2S,3S,4S,5R)-3,4,5-三羟基-6-(5-羟基-4-酮-2-苯基色烯-3-基)氧乙烷-2-羧酸。

3,5-Dihydroxyflavone has known human metabolites that include (2S,3S,4S,5R)-3,4,5-Trihydroxy-6-(5-hydroxy-4-oxo-2-phenylchromen-3-yl)oxyoxane-2-carboxylic acid.

来源:NORMAN Suspect List Exchange

安全信息

• 海关编码：
  2914400090

反应信息

• 作为反应物：
  描述：

  3,5-二羟基黄酮 在 吡啶 、 sodium hydroxide 、 dipotassium peroxodisulfate 、 氢碘酸 、 乙酸酐 、 potassium carbonate 、 丙酮 作用下， 生成 5-hydroxy-3,8-dimethoxy-2-phenyl-chromen-4-one
  参考文献：
  名称：

  Seshadri et al., Proceedings - Indian Academy of Sciences, Section A, 1950, # 32, p. 250,254

  摘要：

  DOI：
• 作为产物：
  描述：

  5-甲氧基黄烷酮 在 盐酸 、 亚硝酸正戊酯 、 乙醇 、 氢碘酸 、 乙酸酐 作用下， 生成 3,5-二羟基黄酮
  参考文献：
  名称：

  Seshadri; Venkateswarlu, Proceedings - Indian Academy of Sciences, Section A, 1947, # 26, p. 189,191

  摘要：

  DOI：

文献信息

• Accurate Prediction of Glucuronidation of Structurally Diverse Phenolics by Human UGT1A9 Using Combined Experimental and In Silico Approaches
  作者：Baojian Wu、Xiaoqiang Wang、Shuxing Zhang、Ming Hu

  DOI：10.1007/s11095-012-0666-z

  日期：2012.6

  Catalytic selectivity of human UGT1A9, an important membrane-bound enzyme catalyzing glucuronidation of xenobiotics, was determined experimentally using 145 phenolics and analyzed by 3D-QSAR methods. Catalytic efficiency of UGT1A9 was determined by kinetic profiling. Quantitative structure activity relationships were analyzed using CoMFA and CoMSIA techniques. Molecular alignment of substrate structures was made by superimposing the glucuronidation site and its adjacent aromatic ring to achieve maximal steric overlap. For a substrate with multiple active glucuronidation sites, each site was considered a separate substrate. 3D-QSAR analyses produced statistically reliable models with good predictive power (CoMFA: q2 = 0.548, r2 = 0.949, r pred 2  = 0.775; CoMSIA: q2 = 0.579, r2 = 0.876, r pred 2  = 0.700). Contour coefficient maps were applied to elucidate structural features among substrates that are responsible for selectivity differences. Contour coefficient maps were overlaid in the catalytic pocket of a homology model of UGT1A9, enabling identification of the UGT1A9 catalytic pocket with a high degree of confidence. CoMFA/CoMSIA models can predict substrate selectivity and in vitro clearance of UGT1A9. Our findings also provide a possible molecular basis for understanding UGT1A9 functions and substrate selectivity.

  通过实验使用145种酚类化合物，并通过3D-QSAR方法分析，确定了人UGT1A9的催化选择性。UGT1A9是一种重要的膜结合酶，催化外源性物质的葡糖醛酸化反应。通过动力学分析确定了UGT1A9的催化效率。使用CoMFA和CoMSIA技术分析了定量结构活性关系。通过将葡糖醛酸化位点及其相邻的芳香环重叠，实现了底物结构的最大立体重叠。对于具有多个活性葡糖醛酸化位点的底物，每个位点被视为单独的底物。3D-QSAR分析产生了统计上可靠的模型，具有良好的预测能力（CoMFA：q2=0.548，r2=0.949，r pred 2=0.775；CoMSIA：q2=0.579，r2=0.876，r pred 2=0.700）。通过轮廓系数图阐明了底物中负责选择性差异的结构特征。将轮廓系数图叠加在UGT1A9的同源模型的催化口袋中，能够高度自信地识别UGT1A9的催化口袋。CoMFA/CoMSIA模型可以预测底物的选择性和UGT1A9的体外清除率。我们的发现还提供了理解UGT1A9功能和底物选择性的可能分子基础。
• Antimicrobial Compounds
  申请人：BIOMERIEUX

  公开号：US20170158720A1

  公开（公告）日：2017-06-08

  An antimicrobial compound, as well as the salts, derivatives and analogues thereof, said compound being represented by the general formula (I): wherein R 1 represents a peptide part P1 or a peptide part P2.

  一种抗微生物化合物，以及其盐、衍生物和类似物，所述化合物由通式（I）表示： 其中R1代表肽部分P1或肽部分P2。
• Three-Dimensional Quantitative Structure-Activity Relationship Studies on UGT1A9-Mediated 3-O-Glucuronidation of Natural Flavonols Using a Pharmacophore-Based Comparative Molecular Field Analysis Model
  作者：Baojian Wu、John Kenneth Morrow、Rashim Singh、Shuxing Zhang、Ming Hu

  DOI：10.1124/jpet.110.175356

  日期：2011.2

  Glucuronidation is often recognized as one of the rate-determining factors that limit the bioavailability of flavonols. Hence, design and synthesis of more bioavailable flavonols would benefit from the establishment of predictive models of glucuronidation using kinetic parameters [e.g., K m, V max, intrinsic clearance (CLint) = V max/ K m] derived for flavonols. This article aims to construct position (3-OH)-specific comparative molecular field analysis (CoMFA) models to describe UDP-glucuronosyltransferase (UGT) 1A9-mediated glucuronidation of flavonols, which can be used to design poor UGT1A9 substrates. The kinetics of recombinant UGT1A9-mediated 3-O-glucuronidation of 30 flavonols was characterized, and kinetic parameters ( K m, V max, CLint) were obtained. The observed K m, V max, and CLint values of 3-O-glucuronidation ranged from 0.04 to 0.68 μM, 0.04 to 12.95 nmol/mg/min, and 0.06 to 109.60 ml/mg/min, respectively. To model UGT1A9-mediated glucuronidation, 30 flavonols were split into the training (23 compounds) and test (7 compounds) sets. These flavonols were then aligned by mapping the flavonols to specific common feature pharmacophores, which were used to construct CoMFA models of V max and CLint, respectively. The derived CoMFA models possessed good internal and external consistency and showed statistical significance and substantive predictive abilities ( V max model: q 2 = 0.738, r 2 = 0.976, r pred2 = 0.735; CLint model: q 2 = 0.561, r 2 = 0.938, rpred2 = 0.630). The contour maps derived from CoMFA modeling clearly indicate structural characteristics associated with rapid or slow 3-O-glucuronidation. In conclusion, the approach of coupling CoMFA analysis with a pharmacophore-based structural alignment is viable for constructing a predictive model for regiospecific glucuronidation rates of flavonols by UGT1A9.

  葡糖醛酸化通常被认为是限制类黄酮醇生物利用度的决定速率的因素之一。因此，利用类黄酮醇的动力学参数（如 Km、Vmax、内在清除率（CLint）= Vmax/ Km）建立葡糖醛酸化的预测模型，将有利于设计合成更多生物可利用的类黄酮醇。本文旨在构建针对3-OH位点的特定比较分子场分析（CoMFA）模型，描述UDP-葡糖醛酸基转移酶（UGT）1A9介导的类黄酮醇葡糖醛酸化过程，该模型可用于设计不佳的UGT1A9底物。我们对重组UGT1A9介导的30种类黄酮醇的3-O-葡糖醛酸化动力学进行了表征，并获得了动力学参数（Km、Vmax、CLint）。观察到的3-O-葡糖醛酸化Km、Vmax和CLint值分别在0.04至0.68 μM、0.04至12.95 nmol/mg/min和0.06至109.60 ml/mg/min之间。为了模拟UGT1A9介导的葡糖醛酸化，我们将30种类黄酮醇分为训练集（23个化合物）和测试集（7个化合物）。然后通过将类黄酮醇映射到特定的共同特征药效团来对齐，从而构建了Vmax和CLint的CoMFA模型。得到的CoMFA模型具有良好的内在和外在一致性，显示出统计学意义和实质性的预测能力（Vmax模型：q2 = 0.738，r2 = 0.976，rpred2 = 0.735；CLint模型：q2 = 0.561，r2 = 0.938，rpred2 = 0.630）。从CoMFA建模得到的轮廓图清晰地表明了与快速或慢速3-O-葡糖醛酸化相关的结构特征。总之，结合CoMFA分析和基于药效团的结构对齐方法是可行的，可以构建用于UGT1A9介导的类黄酮醇区域特异性葡糖醛酸化速率的预测模型。
• COMPOUNDS AND METHODS FOR TREATMENT AND PREVENTION OF FLAVIVIRUS INFECTION
  申请人：FLORIDA STATE UNIVERSITY RESEARCH FOUNDATION, INC.

  公开号：US20180015153A1

  公开（公告）日：2018-01-18

  The present invention concerns the use of compounds for the treatment or prevention of Flavivirus infections, such as Zika virus infections. Aspects of the invention include methods for treating or preventing Flavivirus virus infection, such as Zika virus infection, by administering a compound or class of compound disclosed herein, such as a niclosamide compound, an emricasan compound, a cyclin-dependent kinase inhibitor, a proteasome inhibitor, or a combination of two or more of the foregoing, to a subject in need thereof; methods for inhibiting Flavivirus infections such as Zika virus infections in a cell in vitro or in vivo; pharmaceutical compositions; packaged dosage formulations; and kits for treating or preventing Flavivirus infections, such Zika virus infections.

  本发明涉及化合物用于治疗或预防黄病毒感染，如寨卡病毒感染。该发明的方面包括通过给予本文所披露的化合物或化合物类别，如尼克洛酰胺化合物、恩米卡珊化合物、细胞周期依赖性激酶抑制剂、蛋白酶体抑制剂或前述两种或更多的组合，治疗或预防黄病毒感染，如寨卡病毒感染的方法；在体外或体内抑制黄病毒感染，如寨卡病毒感染的方法；制药组合；包装剂量配方；以及用于治疗或预防黄病毒感染，如寨卡病毒感染的工具包。
• Flavonoids as Synergists for Enhancing the Action of Self-Tanning Substances
  申请人：Rudolph Thomas

  公开号：US20080279793A1

  公开（公告）日：2008-11-13

  The invention relates to the use of at least one flavonoid having an uncharged flavan skeleton as synergist for enhancing the action of self-tanning substances, such as trioses and tetroses, in cosmetic and dermatological formulations and to corresponding novel compositions and to the preparation thereof.

  这项发明涉及在化妆品和皮肤科制剂中使用至少一种具有未带电的黄酮骨架的黄酮类物质作为协同剂，以增强自日晒剂（如三糖和四糖）的作用，并涉及相应的新型组合物及其制备方法。