5,7,2-三羟基黄酮 | 73046-40-9

• 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: 5,7,2-三羟基黄酮
• 英文名称: 5,7,2'-Trihydroxyflavone
• 英文别名: 2',5,7-trihydroxyflavone；5,7-dihydroxy-2-(2-hydroxyphenyl)chromen-4-one
• CAS: 73046-40-9
• 化学式: C₁₅H₁₀O₅
• mdl: MFCD00064915
• 分子量: 270.241
• InChiKey: OFYPDAKTVZXXPC-UHFFFAOYSA-N

物化性质

• 熔点：
  283-285 °C(Solv: ethanol (64-17-5))
• 沸点：
  537.4±50.0 °C(Predicted)
• 密度：
  1.548±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 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

5,7,2'-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-[5-羟基-2-(2-羟基苯基)-4-氧杂色烯-7-基]氧基氧杂环己烷-2-羧酸。

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

来源:NORMAN Suspect List Exchange

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  5,7,2-三羟基黄酮 、 UDP-glucuronic acid 在 human UDP-glucuronosyltransferase 1A₉ 、 magnesium chloride 、 alamethicin 、 糖质酸-1,4-内酯 作用下， 生成 chrysoeriol-7-O-β-D-glucuronide
  参考文献：
  名称：

  Accurate Prediction of Glucuronidation of Structurally Diverse Phenolics by Human UGT1A9 Using Combined Experimental and In Silico Approaches

  摘要：

  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。

  DOI：

  10.1007/s11095-012-0666-z
• 作为产物：
  描述：

  2-乙酰基-3,5-双(苄氧基)苯酚 在 5%-palladium/activated carbon 、 20% palladium hydroxide-activated charcoal 、 氢气 、 碘 、 sodium hydroxide 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 12.5h， 生成 5,7,2-三羟基黄酮
  参考文献：
  名称：

  Flavonoids from Scutellaria baicalensis inhibit senescence-associated secretory phenotype production by interrupting IκBζ/C/EBPβ pathway: Inhibition of age-related inflammation

  摘要：

  Background Prolonged exposure to the senescence-associated secretory phenotype (SASP) with age leads to chronic low-grade inflammation in neighboring cells and tissues, causing many chronic degenerative diseases.Purpose: The effects on SASP production of the ethanol extract from Scutellaria radix and 17 isolated flavonoid constituents were examined in vitro and in vivo.Methods: Cellular senescence was induced by bleomycin. Expression of the SASP and cell signaling molecules was detected using ELISA, RT-qPCR, Western blotting, and immunofluorescence staining. To investigate the in vivo effects, 21-month-old aged rats were used.Results: The ethanol extract and 5 compounds including 1 (Oroxylin A; 5,7-dihydroxy-6-methoxyflavone), 5 (2',6',5,7-tetrahydroxy-8-methoxyflavone), 8 (2',5,7-trihydroxyflavone), 10 (2',5,7-trihydroxy-8-methoxyflavone) and 11 (2',5,7-trihydroxy-6-methoxyflavone) potently reduced IL-6 and IL-8 production and gene expression of the SASP, including IL-1 alpha, IL-1 beta, IL-6, IL-8, GM-CSF, CXCL1, MCP-2, and MMP-3. This finding indicates the important role of the B-ring 2'-hydroxyl group in flavonoid molecules. Furthermore, compounds 8 and 11, the strongest SASP inhibitors, decreased the expression of I kappa B zeta and C/EBP beta protein without affecting either BrdU uptake or the expression of senescence markers, such as pRb and p21. Finally, the oral administration of compound 8 to aged rats at 2 and 4 mg/kg/day for 10 days significantly inhibited the gene expression of SASP and I kappa B zeta in kidneys. This is the first report of the strong SASP inhibitory action of flavonoids from Scutellaria radix on in vitro and in vivo senescence models. The inhibitory action was shown to be mediated mainly by interfering with the I kappa B zeta/C/EBP beta signaling pathway.Conclusion: Targeting production of the SASP using flavonoids from Scutellaria radix or its extract might help reduce low-grade sterile inflammation and control age-related diseases.

  DOI：

  10.1016/j.phymed.2020.153255

文献信息

• Synthetic flavonoid derivatives targeting the glycogen phosphorylase inhibitor site: QM/MM-PBSA motivated synthesis of substituted 5,7-dihydroxyflavones, crystallography, in vitro kinetics and ex-vivo cellular experiments reveal novel potent inhibitors
  作者：Ben A. Chetter、Efthimios Kyriakis、Daniel Barr、Aikaterini G. Karra、Elisabeth Katsidou、Symeon M. Koulas、Vassiliki T. Skamnaki、Timothy J. Snape、Anna-Maria G. Psarra、Demetres D. Leonidas、Joseph M. Hayes

  DOI：10.1016/j.bioorg.2020.104003

  日期：2020.9

  agents. Flavonoids are novel inhibitors of GP, but their mode of action is unspecific in terms of the GP binding sites involved. Towards design of synthetic flavonoid analogues acting specifically at the inhibitor site and to exploit the site’s hydrophobic pocket, chrysin has been employed as a lead compound for the in silico screening of 1169 new analogues with different B ring substitutions. QM/MM-PBSA

  糖原磷酸化酶（GP）是开发新型抗高血糖药的重要目标。黄酮类化合物是GP的新型抑制剂，但是它们的作用方式在涉及的GP结合位点方面没有特异性。为了设计专门作用于抑制剂位点的合成类黄酮类似物，并利用该位点的疏水口袋，采用了菊花蛋白作为先导化合物，用于计算机筛选1169种具有不同B环取代的新类似物。QM / MM-PBSA结合自由能的计算指导了8种化合物的最终选择，随后使用Baker-Venkataraman重排-环化方法进行合成。针对兔肌肉GPa和GPb以及人肝脏GPa的动力学实验揭示了其中的三种化合物（11，20和43）中的最有效的，其结合在现场（ķ我小号<4μM对于所有三种同种型），和比以前更有效报道的天然类黄酮抑制剂。多次抑制研究表明，仅在抑制剂位点结合。该结合与葡萄糖是协同的，表明抑制作用可以通过血糖水平来调节，并且随着达到正常血糖而降低。化合物43是肝细胞糖原分解的有效抑制剂（IC 50
• [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。
• Anti-glycation agents for preventing age- diabetes- and smoking-related complications
  申请人：Yeboah Faustinus

  公开号：US20050043408A1

  公开（公告）日：2005-02-24

  The invention provides new inhibitors of protein glycation, identified from compound libraries by a high throughput screening assay. The anti-glycation agents so identified are characterized by a variety of chemical structures and are useful for the prevention or treatment of age-, diabetes-, and smoking-related complications, including neuropathy, nephropathy, ocular pathologies, or the loss of mechanical properties of collagenous tissues. Among compounds identified as having the anti-glycation activity, of special interest are epinephrine and its analogs, in particular D-epinephrine and its analogs, which are particularly useful for the prevention or treatment of age-, diabetes-, and smoking-related ocular pathologies.

  这项发明提供了新的蛋白质糖基化抑制剂，通过高通量筛选检测从化合物库中鉴定出来。所鉴定的抗糖基化剂具有多种化学结构，可用于预防或治疗与年龄、糖尿病和吸烟有关的并发症，包括神经病变、肾病、眼部病理或胶原组织的机械性能丧失。在被鉴定为具有抗糖基化活性的化合物中，特别感兴趣的是肾上腺素及其类似物，特别是D-肾上腺素及其类似物，可用于预防或治疗与年龄、糖尿病和吸烟有关的眼部病理。
• ANTI-GLYCATION AGENTS FOR PREVENTING AGE-, DIABETES-, AND SMOKING-RELATED COMPLICATIONS
  申请人：YEBOAH Faustinus

  公开号：US20080139664A1

  公开（公告）日：2008-06-12

  The invention provides new inhibitors of protein glycation, identified from compound libraries by a high throughput screening assay. The anti-glycation agents so identified are characterized by a variety of chemical structures and are useful for the prevention or treatment of age-, diabetes-, and smoking-related complications, including neuropathy, nephropathy, ocular pathologies, or the loss of mechanical properties of collagenous tissues. Among compounds identified as having the anti-glycation activity, of special interest are epinephrine and its analogs, in particular D-epinephrine and its analogs, which are particularly useful for the prevention or treatment of age-, diabetes-, and smoking-related ocular pathologies.

  该发明提供了新的蛋白质糖基化抑制剂，通过高通量筛选检测从化合物库中确定。所确定的抗糖基化剂具有各种化学结构，并可用于预防或治疗与年龄、糖尿病和吸烟相关的并发症，包括神经病变、肾病、眼部病理或胶原组织机械性能的丧失。在被确定为具有抗糖基化活性的化合物中，特别感兴趣的是肾上腺素及其类似物，特别是D-肾上腺素及其类似物，这些物质特别适用于预防或治疗与年龄、糖尿病和吸烟相关的眼部病理。
• Method and system for effecting changes in pigmented tissue
  申请人：Moazed Kambiz Thomas

  公开号：US20120207809A1

  公开（公告）日：2012-08-16

  Methods and systems are described for a rapid and sustainable change in the pigment melanin content of melanocytes of the iris stroma, thereby to change the color of the eye. Also described are compositions for lightening or darkening the pigmented tissues or treating a pigmented tissue disease.

  本文描述了一种快速和可持续改变虹膜基质黑素细胞中黑色素含量的方法和系统，从而改变眼睛的颜色。还描述了用于使色素组织变浅或变深或治疗色素组织疾病的组合物。