3,7-dihydroxy-2-(3-hydroxyphenyl)-4H-chromen-4-one | 151698-64-5

• 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: 3,7-dihydroxy-2-(3-hydroxyphenyl)-4H-chromen-4-one
• 英文别名: 7,3'-dihydroxyflavonol；3,7,3'-Trihydroxyflavone；3,7-dihydroxy-2-(3-hydroxyphenyl)chromen-4-one
• CAS: 151698-64-5
• 化学式: C₁₅H₁₀O₅
• 分子量: 270.241
• InChiKey: PSGKFXVPVUNGDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 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：
  87
• 氢给体数：
  3
• 氢受体数：
  5

ADMET

代谢

3,7,3p-三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-[7-羟基-2-(3-羟基苯基)-4-氧代色原-3-基]氧杂环己烷-2-羧酸。

3,7,3p-Trihydroxyflavone has known human metabolites that include (2S,3S,4S,5R)-3,4,5-trihydroxy-6-[7-hydroxy-2-(3-hydroxyphenyl)-4-oxochromen-3-yl]oxyoxane-2-carboxylic acid.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  3,7-dihydroxy-2-(3-hydroxyphenyl)-4H-chromen-4-one 在 三甲基铵三氧化硫共聚物 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  Discovery of novel sulfonated small molecules that inhibit vascular tube formation

  摘要：

  Tumor-associated angiogenesis is a complex process that involves the interplay among several molecular players such as cell-surface heparan sulfate proteoglycans, vascular endothelial growth factors and their cognate receptors. PI-88, a highly sulfonated oligosaccharide, has been shown to have potent anti-angiogenic activity and is currently in clinical trials. However, one of the major drawbacks of large oligosaccharides such as PI-88 is that their synthesis often requires numerous complex synthetic steps. In this study, several novel polysulfonated small molecule carbohydrate mimetics, which can easily be synthesized in fewer steps, are identified as promising inhibitors of angiogenesis in an in vitro tube formation assay. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.014
• 作为产物：
  描述：

  1-(2,4-二羟基苯基)-2-甲氧基-1-乙酮 在 氢碘酸 、 sodium 3-methoxybenzoate 作用下， 生成 3,7-dihydroxy-2-(3-hydroxyphenyl)-4H-chromen-4-one
  参考文献：
  名称：

  981.螯合系统。第二部分

  摘要：

  DOI：

  10.1039/jr9520005027

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。
• Profiling of Flavonol Derivatives for the Development of Antitrypanosomatidic Drugs
  作者：Chiara Borsari、Rosaria Luciani、Cecilia Pozzi、Ina Poehner、Stefan Henrich、Matteo Trande、Anabela Cordeiro-da-Silva、Nuno Santarem、Catarina Baptista、Annalisa Tait、Flavio Di Pisa、Lucia Dello Iacono、Giacomo Landi、Sheraz Gul、Markus Wolf、Maria Kuzikov、Bernhard Ellinger、Jeanette Reinshagen、Gesa Witt、Philip Gribbon、Manfred Kohler、Oliver Keminer、Birte Behrens、Luca Costantino、Paloma Tejera Nevado、Eugenia Bifeld、Julia Eick、Joachim Clos、Juan Torrado、María D. Jiménez-Antón、María J. Corral、José M Alunda、Federica Pellati、Rebecca C. Wade、Stefania Ferrari、Stefano Mangani、Maria Paola Costi

  DOI：10.1021/acs.jmedchem.6b00698

  日期：2016.8.25

  Flavonoids represent a potential source of new antitrypanosomatidic leads. Starting from a library of natural products, we combined target-based screening on pteridine reductase 1 with phenotypic screening on Trypanosoma brucei for hit identification. Flavonols were identified as hits, and a library of 16 derivatives was synthesized. Twelve compounds showed EC50 values against T. brucei below 10 μM

  黄酮类化合物代表了新的抗胰蛋白酶前导物的潜在来源。从天然产物库开始，我们将基于靶点的蝶呤还原酶1筛选与基于布鲁氏锥虫的表型筛选相结合，以进行命中鉴定。黄酮醇被鉴定为命中，并合成了16种衍生物的文库。十二种化合物对布鲁氏杆菌的EC 50值低于10μM。四个X射线晶体结构和对接研究解释了观察到的结构与活性之间的关系。选择化合物2（3，6-二羟基-2-（3-羟基苯基）-4 H-铬-4--4-酮）进行药代动力学研究。化合物2的包封与游离化合物相比，PLGA纳米颗粒或环糊精中的α-己内酰胺导致较低的体外毒性。与甲氨蝶呤的组合研究表明，化合物13（3-羟基-6-甲氧基-2-（4-甲氧基苯基）-4 H-铬烯-4-酮）在浓度为1.3μM时具有最高的协同作用，剂量降低了11.7倍指数，对宿主细胞无毒性。我们的结果为进一步的化学修饰提供了基础，这些化学修饰旨在鉴定出对PTR1表现出更高效力并提高了代谢稳定性的新型抗胰体分裂素药物。
• On the antioxidant properties of three synthetic flavonols
  作者：Montana、Pappano、Giordano、Molina、Debattista、Garcia, Norman A.

  DOI：10.1691/ph.2007.1.6559

  日期：——

  The antioxidant properties of a series of synthetic and natural flavonoids towards the oxygenated species superoxide radical anion (O2 ·—) enzimatically generated, were evaluated. 7-Hydroxyflavonol, 7,3′-dihydroxyflavonol and 3′-hydroxyflavonol were synthesised, with a systematic variation of the OH substitution on positions C3, C7, C3′and C4′, and their respective antioxidative abilities compared to those of the already characterised natural flavonoids quercetin, kaempferol and rutin. The efficiency of O2 ·— deactivation by the flavonoids does not correlate with their respective determined oxidation potentials, suggesting that the pure one-electron-transfer-mechanism of O2 ·— quenching could not be the main scavenging process involved. Experimental evidence demonstrated that the possible inhibition of the O2 ·—-generator enzymatic system by the flavonoids must be disregarded as a possible indirect cause for the inhibition of the oxidative species. One possible mechanism for the inhibition of O2 ·—, highly dependent on the substitution pattern of the flavonoid, may be the generation of hydroperoxides or dioxetanes as oxidation products, as already postulated for other biologically relevant compounds. The simultaneous OH-substitution on positions C3 and C7 of the flavonoid skeleton plays a definitive role in the enhancement of the O2 ·— inhibitory effect. The replacement of OH by a O-rutinosyl group on position C7 suppresses at all that effect, whereas the absence of an OH group in position 7 significantly reduces the antioxidative power. Finally, the presence of OH groups on positions 3′and 4′ does not produce any determinant effect in the antioxidative behaviour of the flavonoids.

  评估了一系列合成和天然类黄酮对酶促产生的含氧物质超氧阴离子（O2·—）的抗氧化特性。7-羟基黄酮、7,3′-二羟基黄酮和3′-羟基黄酮在C3、C7、C3′和C4′位置上的羟基取代存在系统变化，并分别与已鉴定的天然类黄酮槲皮素、山奈酚和芦丁的抗氧化能力进行了比较。类黄酮对O2·—的失活效率与其各自的氧化电位无关，表明O2·—淬灭的纯一电子转移机制可能不是主要的清除过程。实验证据表明，类黄酮对O2·—生成酶系统的可能抑制作用不应被视为氧化物质抑制的间接原因。抑制O2·—的一种可能机制高度依赖于类黄酮的取代模式，可能与生成过氧化氢或二氧杂环丁烷作为氧化产物有关，正如其他生物相关化合物所假设的那样。类黄酮骨架上C3和C7位置同时发生羟基取代在增强O2·—抑制作用方面起着决定性作用。C7位置上的羟基被O-芦丁基取代会抑制这种作用，而7位置没有羟基会显著降低抗氧化能力。最后，3′和4′位置上的羟基不会
• Combination therapies for the treatment of Alzheimer's disease and related disorders
  申请人：The General Hospital Corporation

  公开号：US10398704B2

  公开（公告）日：2019-09-03

  The present invention relates to combination therapies for treating Alzheimer's disease or an amyloidosis-associated pathological condition comprising co-administering a therapeutically effective amount of a first compound, and a therapeutically effective amount of a second compound. In certain embodiments, the first compound or the second compound inhibits AB peptide polymerization; is an anti-inflammatory; improves cognitive function, mood, or social behavior; is associated with Tau or alpha-synuclein; or regulates amyloid peptide washout.

  本发明涉及治疗阿尔茨海默氏症或淀粉样变性相关病理状况的组合疗法，包括联合施用治疗有效量的第一种化合物和治疗有效量的第二种化合物。在某些实施方案中，第一种化合物或第二种化合物抑制AB肽聚合；抗炎；改善认知功能、情绪或社会行为；与Tau或α-突触核蛋白相关；或调节淀粉样肽冲洗。
• Combination therapies for the treatment of alzheimer's disease and related disorders
  申请人：The General Hospital Corporation

  公开号：US11110097B2

  公开（公告）日：2021-09-07

  The present invention relates to combination therapies for treating Alzheimer's disease or an amyloidosis-associated pathological condition comprising co-administering a therapeutically effective amount of a first compound, and a therapeutically effective amount of a second compound. In certain embodiments, the first compound or the second compound inhibits AB peptide polymerization; is an anti-inflammatory; improves cognitive function, mood, or social behavior; is associated with Tau or alpha-synuclein; or regulates amyloid peptide washout.

  本发明涉及治疗阿尔茨海默氏症或淀粉样变性相关病理状况的组合疗法，包括联合施用治疗有效量的第一种化合物和治疗有效量的第二种化合物。在某些实施方案中，第一种化合物或第二种化合物抑制AB肽聚合；抗炎；改善认知功能、情绪或社会行为；与Tau或α-突触核蛋白相关；或调节淀粉样肽冲洗。