7-hydroxy-2-(p-tolyl)-4H-chromen-4-one | 78298-69-8

• 物质功能分类: 医药中间体 - 原料药中间体
• 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: 7-hydroxy-2-(p-tolyl)-4H-chromen-4-one
• 英文别名: 7-hydroxy-4'-methylflavone；7-hydroxy-2-(4-methylphenyl)-4H-chromen-4-one；4'-Methyl-7-hydroxyflavone；7-hydroxy-2-p-tolyl-chromen-4-one；7-Hydroxy-2-p-tolyl-chromen-4-on；7-hydroxy-2-(4-methylphenyl)chromen-4-one
• CAS: 78298-69-8
• 化学式: C₁₆H₁₂O₃
• 分子量: 252.269
• InChiKey: AZXPROVWHNKILY-UHFFFAOYSA-N

物化性质

• 熔点：
  278-280 °C(Solv: ethanol (64-17-5))
• 沸点：
  458.8±45.0 °C(Predicted)
• 密度：
  1.300±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-hydroxy-2-(p-tolyl)-4H-chromen-4-one 在 三氯硫磷 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  基于磷酸盐和硫代磷酸黄酮类似物的类固醇硫酸酯酶抑制剂。

  摘要：

  临床前研究

  DOI：

  10.1002/ddr.21281
• 作为产物：
  描述：

  丹皮酚 在 碘 、 吡啶盐酸盐 、 potassium hydroxide 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 10.0h， 生成 7-hydroxy-2-(p-tolyl)-4H-chromen-4-one
  参考文献：
  名称：

  基于磷酸盐和硫代磷酸黄酮类似物的类固醇硫酸酯酶抑制剂。

  摘要：

  临床前研究

  DOI：

  10.1002/ddr.21281

文献信息

• Synthesis and Antiproliferative Activity of Some Dihydro-1H-furo[2,3-c]pyrazole-Flavone Hybrids
  作者：Venkata Swamy Tangeti、D. Vasundhara、K.V.V.V. Satyanarayana、Kaja Srinivas Pavan Kumar

  DOI：10.14233/ajchem.2017.20550

  日期：——

  A new series of dihydro-1H-furo[2,3-c]pyrazole-flavone hybrids were synthesized from one-pot four-component reaction of b-keto ester (1), hydrazine (2), 7-hydroxy 8-formyl flavones (3), pyridiniumylide (4) in presence of NEt3 as catalyst under ethanol reflux conditions and their antiproliferative properties were evaluated against human cancer cell lines, namely, laryngeal carcinoma (Hep2), lung adenocarcinoma (A549) and cervical cancer (HeLa). The best among them, furo[2,3-c]pyrazole-flavone with C4-methoxy substitution was selected for further structure activity relationship (SAR) studies. Among the derivatives, (4S,5S)-ethyl 4-(7-hydroxy-5-methoxy-4-oxo-2-(2,4,6-trimethoxyphenyl)-4H-chromen-8-yl)-3-methyl-4,5-dihydro-1H-furo[2,3-c]pyrazole-5-carboxylate (8r) showed most potent cytotoxic activity against all three cancer cell lines. Toxicity studies revealed that the dihydro-1H-furo[2,3-c]pyrazole-flavones are specifically target the cancer cell lines.

  一系列二氢-1H-呋喃[2,3-c]吡唑-黄酮杂合物通过一锅四组分反应合成，反应物包括β-酮酯（1）、肼（2）、7-羟基-8-醛黄酮（3）和吡啶亚胺（4），在三乙胺（NEt3）催化下于乙醇回流条件下进行。随后评估了这些化合物对人类癌细胞系的抗增殖活性，包括喉癌（Hep2）、肺腺癌（A549）和宫颈癌（HeLa）。在这些化合物中，C4-取代的甲氧基二氢-1H-呋喃[2,3-c]吡唑-黄酮被选为进一步结构-活性关系（SAR）研究的对象。在这些衍生物中，(4S,5S)-乙基4-(7-羟基-5-甲氧基-4-氧基-2-(2,4,6-三甲氧基苯基)-4H-香豆烯-8-基)-3-甲基-4,5-二氢-1H-呋喃[2,3-c]吡唑-5-羧酸酯（8r）对所有三种癌细胞系表现出最强的细胞毒活性。毒性研究表明，二氢-1H-呋喃[2,3-c]吡唑-黄酮特别靶向癌细胞系。
• An Efficient One-Pot Synthesis and Anticancer Activity of 4'-Substituted Flavonoids
  作者：X. Wang、J. Liu、Y. Zhang

  DOI：10.1134/s1070363218050328

  日期：2018.5

  A number of 4'-substituted (R = H, Me, Cl, F) flavone derivatives is synthesized from 2-hydroxyacetophenones using the modified Baker–Venkataraman reaction. Compound [3-(4-fluorobenzoyl)-5- hydroxy-4'-fluoroflavone] was synthesized for the first time with the yield of 12%. Antiproliferative assays indicate that the synthesized flavones with F substituent at the 4' position demonstrate higher activity

  使用修饰的Baker-Venkataraman反应，由2-羟基苯乙酮合成了许多4'-取代的（R = H，Me，Cl，F）黄酮衍生物。首次合成化合物[3-（4-氟苯甲酰基）-5-羟基-4'-氟黄酮]，产率为12％。抗增殖试验表明，合成的黄酮在4'位具有F取代基，显示出比其他黄酮衍生物更高的活性，特别是针对HeLa和MCF-7的IC 50为9.5和2.7μM。
• Design, synthesis and apoptosis inducing activity of nonsteroidal flavone-methanesulfonate derivatives on MCF-7 cell line as potential sulfatase inhibitor
  作者：Mahdiyeh H. S. Javadi、Aida Iraji、Maliheh Safavi、Hamed Montazeri、Parastoo Tarighi、Samane Eftekhari、Latifeh Navidpour、Seyedeh Sara Mirfazli

  DOI：10.1007/s00044-021-02767-w

  日期：2021.9

  optimization was conducted to design novel flavone-sulfonates pharmacophore as a new steroid sulfatase inhibitor. In the present work, the conventional methods for the synthesis of 4-oxo-2-phenyl-4H-chromen-7-yl methanesulfonate derivatives were reported. Their cytotoxicity was evaluated with MTT assay against a breast cancer cell line (MCF-7). The apoptosis inducing activity of the most cytotoxic compound

  近年来，专注于具有选择性活性的新型强效抗癌药物是癌症治疗的最大挑战之一。乳腺癌是最常见的癌症，也是女性癌症死亡的主要原因。硫酸酯酶在将硫酸化类固醇转化为非硫酸化类固醇激素方面发挥着重要作用，这会增加许多激素依赖性癌症（如乳腺癌）的生长和发展。在这方面，进行了基于结构的优化以设计新的黄酮磺酸盐药效团作为新的类固醇硫酸酯酶抑制剂。在目前的工作中，合成 4-oxo-2-phenyl-4 H的常规方法报道了-chromen-7-yl 甲磺酸酯衍生物。它们的细胞毒性通过 MTT 测定对乳腺癌细胞系 (MCF-7) 进行评估。在雌二醇是癌细胞存活的关键生长因子的情况下，与多西紫杉醇相比，评估了最具细胞毒性的化合物3c的凋亡诱导活性，IC 50值为 0.615 µM。双染色Annexin V-FITC/PI分析结果表明该化合物3c在MCF-7细胞中的细胞毒活性通过细胞凋亡发生。进行了分子对接研究以阐明最有希望的化合物（3c）的抑制模式)
• Identification of bicyclic compounds that act as dual inhibitors of Bcl-2 and Mcl-1
  作者：Abhay Uthale、Aarti Anantram、Prasad Sulkshane、Mariam Degani、Tanuja Teni

  DOI：10.1007/s11030-022-10494-6

  日期：——

  Elevated expression of anti-apoptotic proteins, such as Bcl-2 and Mcl-1 contributes to poor prognosis and resistance to current treatment modalities in multiple cancers. Here, we report the design, synthesis and characterization of benzimidazole chalcone and flavonoid scaffold-derived bicyclic compounds targeting both Bcl-2 and Mcl-1 by optimizing the structural differences in the binding sites of both these proteins. Initial docking screen of Bcl-2 and Mcl-1 with pro-apoptotic protein Bim revealed possible hits with optimal binding energies. All the optimized bicyclic compounds were screened for their in vitro cytotoxic activity against two oral cancer cell lines (AW8507 and AW13516) which express high levels of Bcl-2 and Mcl-1. Compound 4d from the benzimidazole chalcone series and compound 6d from the flavonoid series exhibited significant cytotoxic activity (IC50 7.12 μM and 17.18 μM, respectively) against AW13516 cell line. Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) analysis further demonstrated that compound 4d and compound 6d could effectively inhibit the Bcl-2 and Mcl-1 proteins by displacing their BH3 binding partners. Both compounds exhibited potent activation of canonical pathway of apoptosis evident from appearance of cleaved Caspase-3 and PARP. Further, treatment of oral cancer cells with the inhibitors induced dissociation of the BH3 only protein Bim from Mcl-1 and Bak from Bcl-2 but failed to release Bax from Bcl-xL thereby confirming the nature of compounds as BH3-mimetics selectively targeting Bcl-2 and Mcl-1. Our study thus identifies bicyclic compounds as promising candidates for anti-apoptotic Bcl-2/Mcl-1 dual inhibitors with a potential for further development.

  抗凋亡蛋白（如Bcl-2和Mcl-1）的表达升高会导致多种癌症预后不良，并导致对现有治疗方式的耐药性。在此，我们报告了苯并咪唑查尔酮和黄酮类化合物骨架衍生物双环化合物的设计、合成和表征，这些化合物通过优化Bcl-2和Mcl-1结合位点的结构差异，同时靶向这两种蛋白。通过将Bcl-2和Mcl-1与促凋亡蛋白Bim进行初步对接筛选，我们发现了具有最佳结合能的可能的靶向化合物。对所有优化后的双环化合物进行了体外细胞毒性活性筛选，以检测其对两种表达高水平Bcl-2和Mcl-1的口腔癌细胞系（AW8507和AW13516）的细胞毒性活性。苯并咪唑查尔酮系列中的化合物4d和黄酮类化合物系列中的化合物6d对AW13516细胞系表现出显著的细胞毒性活性（IC50分别为7.12 μM和17.18 μM）。时间分辨荧光共振能量转移（TR-FRET）分析进一步表明，化合物4d和化合物6d可通过置换其BH3结合伴侣来有效抑制Bcl-2和Mcl-1蛋白。从裂解的Caspase-3
• Palladium-catalyzed regioselective arylation of 7-hydroxyflavone with diaryliodonium salts
  作者：Yu-Ping Zhao、Jia-Lu Liao、Chen-Fu Liu

  DOI：10.1016/j.tetlet.2023.154573

  日期：2023.6

  A palladium-catalyzed regioselective arylation at the C6 position of 7-hydroxyflavone protocol was disclosed for the first time. The reaction occurs in carbamate directing group directed CH activation manner. The key to this high regioselectivity is the appropriate choice of carbamates as protecting/directing groups and H3PO4 additive in the presence of Pd (TFA)2 catalyst. Additionally, the procedure

  首次公开了钯催化的 7-羟基黄酮 C6 位区域选择性芳基化方案。该反应以氨基甲酸酯导向基团定向的CH活化方式发生。这种高区域选择性的关键是2存在下3PO4。此外，该程序为制备 6-芳基黄酮衍生物提供了一种权宜之计。