2-(3,4-二甲氧苯基)-3-羟基-4H-吡喃-4-酮 | 6889-80-1

• 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: 2-(3,4-二甲氧苯基)-3-羟基-4H-吡喃-4-酮
• 英文名称: 2-(3,4-dimethoxyphenyl)-3-hydroxy-4H-chromen-4-one
• 英文别名: 3',4'-Dimethoxyflavonol；3-hydroxy-3',4'-dimethoxyflavone；2-(3,4-dimethoxyphenyl)-3-hydroxychromen-4-one
• CAS: 6889-80-1
• 化学式: C₁₇H₁₄O₅
• 分子量: 298.295
• InChiKey: BXLAVJWSFYZDPF-UHFFFAOYSA-N

物化性质

• 碰撞截面：
  164.1 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  2-8°C，干燥

反应信息

• 作为反应物：
  描述：

  2-(3,4-二甲氧苯基)-3-羟基-4H-吡喃-4-酮 在 氢碘酸 作用下， 以44%的产率得到3,3’,4’-三羟基黄酮
  参考文献：
  名称：

  Effect of Flavonol Derivatives on the Carrageenin-Induced Paw Edema in the Rat and Inhibition of Cyclooxygenase-1 and 5-Lipoxygenasein Vitro

  摘要：

  Alkoxyflavonols were synthesized by the Algar-Flynn-Oyamada (AFO) cyclization of chalcones. Hydroxyflavonols were prepared by dealkylation of methoxyflavonols by refluxing in hydroiodic acid. The alkoxyflavonols 3-hydroxy-2-(2,3,4-trimethoxyphenyl)-4H-chromen-4-one (6), 2-(4-ethoxyphenyl)-3-hydroxy-4H-chromen-4-one (7), 2-(4-butoxyphenyl)-3-hydroxy-4H-chromen-4-one (10), and 2-(3-n-butoxyphenyl)-3-hydroxy-4H-chromen-4-one (11) as well as the trihydroxy derivative 3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4H-chromen-4-one (18) displayed high anti-inflammatory activity in carrageenin-induced rat paw edema. Additionally, the inhibition of enzymes of the arachidonic acid cascade by the derivatives was investigated in vitro. In contrast to the natural compound quercetin, the compounds were more potent inhibiting cyclooxygenase-1 than 5-lipoxygenase except for 3-hydroxy-7-methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one (5). No correlation between the anti-inflammatory activity in the rat paw edema test and the inhibition of 5-lipoxygenase or cyclooxygenase-1 could be observed. In conclusion, the present results suggest that other effects than inhibition of these enzymes of the arachidonic acid cascade are important for the anti-inflammatory activity of the investigated alkoxyflavonols.

  DOI：

  10.1002/1521-4184(20007)333:7<205::aid-ardp205>3.0.co;2-y
• 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 作用下， 以 乙醇 为溶剂， 生成 2-(3,4-二甲氧苯基)-3-羟基-4H-吡喃-4-酮
  参考文献：
  名称：

  Exploring the anti-breast cancer potential of flavonoid analogs

  摘要：

  在寻找新的乳腺癌抗肿瘤药物的过程中，合成了新的黄酮衍生物，并对其进行了表征，并检测其对乳腺癌细胞系的抗肿瘤活性。

  DOI：

  10.1039/c6ra14428d

文献信息

• Design, synthesis, and biological evaluation of <i>Helicobacter pylori</i> inosine 5′-monophosphate dehydrogenase (<i>Hp</i> IMPDH) inhibitors
  作者：Niteshkumar U. Sahu、Gayathri Purushothaman、Vijay Thiruvenkatam、Prashant S. Kharkar

  DOI：10.1002/ddr.21467

  日期：2019.2

  Inosine 5′‐monophosphate dehydrogenase (IMPDH) catalyzes a crucial step in the biosynthesis of guanine nucleotides. Being a validated target for immunosuppressive, antiviral, and anticancer drug development, lately it has been exploited as a promising target for antimicrobial therapy. Extending our previous work on Mycobacterium tuberculosis IMPDH, GuaB2, inhibitor development, we screened a set of

  肌苷5'-单磷酸脱氢酶（IMPDH）催化鸟嘌呤核苷酸生物合成中的关键步骤。作为免疫抑制，抗病毒和抗癌药物开发的有效靶标，最近它已被用作抗菌治疗的有希望的靶标。扩展了我们先前关于结核分枝杆菌IMPDH，GuaB2，抑制剂开发的工作，我们筛选了23种新的化学实体（NCE），它们被取代的黄酮（系列1）和1,2,3-三唑（系列2）核心结构所取代。体外幽门螺杆菌IMPDH（Hp IMPDH）和人IMPDH2（h IMPDH2）的抑制活性。所有NCE都具有可接受的分子，物理化学和毒性特性。的范围在10μM浓度下，Hp IMPDH和h IMPDH2的抑制分别为9–99.9％和16–57％。最有效的Hp IMPDH抑制剂25c的IC 50值为1.27μM ，无h IMPDH2抑制活性。中等强度，结构新颖的命中分子25c可作为进一步设计和开发高效Hp IMPDH抑制剂的先导。
• Discovery of a Prenylated Flavonol Derivative as a Pin1 Inhibitor to Suppress Hepatocellular Carcinoma by Modulating MicroRNA Biogenesis
  作者：Yuanyuan Zheng、Wenchen Pu、Jiao Li、Xianyan Shen、Qiang Zhou、Xin Fan、Sheng-Yong Yang、Yamei Yu、Qiang Chen、Chun Wang、Xin Wu、Yong Peng

  DOI：10.1002/asia.201801461

  日期：2019.1.4

  isomerase Pin1 plays a crucial role in the development of human cancers. Recently, we have disclosed that Pin1 regulates the biogenesis of miRNA, which is aberrantly expressed in HCC and promotes HCC progression, indicating the therapeutic role of Pin1 in HCC therapy. Here, 7‐(benzyloxy)‐3,5‐dihydroxy‐2‐(4‐methoxyphenyl)‐8‐(3‐methylbut‐2‐en‐1‐yl)‐4H‐chromen‐4‐one (AF‐39) was identified as a novel Pin1

  肽脯氨酰顺-反异构酶中Pin1在人类癌症的发展至关重要的作用。最近，我们披露了Pin1调节miRNA的生物发生，miRNA在HCC中异常表达并促进HCC进展，表明Pin1在HCC治疗中的治疗作用。在此，7-（苄氧基）-3,5-二羟基-2-（4-甲氧基苯基）-8-（3-甲基丁-2-烯-1-基）-4H-铬-4--1（AF-39）被鉴定为新型的Pin1抑制剂。生化试验表明，AF-39有效抑制中Pin1活性，其IC 50的1.008μ值米，并且还显示中肽基脯氨酰异构酶对中Pin1高选择性。此外，AF‐39以剂量和时间依赖性方式显着抑制HCC细胞的细胞增殖。从机制上讲，AF-39调节XPO5的亚细胞分布并增加HCC细胞中miRNA的生物发生。这项工作为HCC治疗提供了有希望的先导化合物，突出了基于miRNA的疗法对人类癌症的治疗潜力。
• Ruthenium(II)-Catalyzed Synthesis of Spirobenzofuranones by a Decarbonylative Annulation Reaction
  作者：Partha P. Kaishap、Gauri Duarah、Bipul Sarma、Dipak Chetia、Sanjib Gogoi

  DOI：10.1002/anie.201710049

  日期：2018.1.8

  activation of six‐membered compounds is reported. The Ru‐catalyzed reaction of 3‐hydroxy‐2‐phenyl‐chromones with alkynes works most efficiently in the presence of the ligand PPh3 to provide spiro‐indenebenzofuranones. Unlike previously reported metal‐catalyzed decarbonylative annulation reactions, in the present decarbonylative annulation reaction, the annulation occurs before extrusion of carbon monoxide

  据报道，炔烃通过六元化合物的C / H / C-C活化而首次脱羰基插入。在配体PPh 3存在下，Ru-催化的3-羟基-2-苯基色酮与炔烃的反应最有效，可提供螺茚二苯并呋喃酮。与以前报道的金属催化的脱羰环化反应不同，在本脱羰环化反应中，环化发生在一氧化碳挤出之前。
• A Mild and Efficient Protocol for the Protection of 3-Hydroxychromones Under Phase-Transfer Catalysis
  作者：Alain Burger、Dmytro Dziuba、Rachid Benhida

  DOI：10.1055/s-0030-1260034

  日期：2011.7

  A mild and efficient protocol for the introduction of different protecting groups on 3-hydroxychromones (3-HCs) under phase-transfer catalysis conditions in toluene or dichloromethane/aqueous potassium hydroxide system in the presence of crown ether has been developed. The method is useful for the protection of base-sensitive chromone derivatives. Protected chromones are easier to handle and to purify

  已经开发了一种温和有效的方案，用于在冠醚存在下在甲苯或二氯甲烷/氢氧化钾水溶液中的相转移催化条件下在3-羟基色酮（3-HCs）上引入不同的保护基。该方法对于保护对碱敏感的色酮衍生物是有用的。受保护的色酮更易于处理和纯化，因此适合进一步的化学转化。使用标准条件干净地裂解保护基。 3-羟基色酮-相转移催化-保护基-酰化-烷基化-裂解
• Superior anticancer activity of halogenated chalcones and flavonols over the natural flavonol quercetin
  作者：Tatiana A. Dias、Cecília L. Duarte、Cristovao F. Lima、M. Fernanda Proença、Cristina Pereira-Wilson

  DOI：10.1016/j.ejmech.2013.04.064

  日期：2013.7

  chalcones whereas for flavonol derivatives the best performance was registered for the 4-substituted derivatives. Flow cytometry analysis showed that compounds 3p and 4o induced cell cycle arrest and apoptosis as demonstrated by increased S, G2/M and sub-G1 phases. These data were corroborated by western blot and fluorescence microscopy analysis. In summary, halogenated chalcones and flavonols were successfully

  通过生态友好的方法以高收率合成了一系列查尔酮和黄酮醇衍生物。用人结肠直肠癌细胞系HCT116进行药理评估，结果表明黄酮醇的抗癌活性高于查尔酮前体的抗癌活性。卤代衍生物的抗增殖活性随着B环的3-位或4-位正位的取代基从F到Cl和Br的增加而增加。此外，位置3的卤素增强了查耳酮的抗癌活性，而对于黄酮醇衍生物而言，4-取代衍生物的最佳性能则得到了证明。流式细胞仪分析表明化合物3p和4oS，G2 / M和sub-G1期增加证明细胞周期阻滞和凋亡。这些数据通过蛋白质印迹和荧光显微镜分析得到证实。总之，成功制备了卤代查耳酮和黄酮醇，并表现出很高的抗癌活性，如它们的细胞生长和对HCT116细胞的细胞周期抑制潜能（优于槲皮素）所显示的那样，它们被用作阳性对照。