2-hydroxy-4,6-dimethoxy-4'-fluorochalcone | 720676-01-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 2-hydroxy-4,6-dimethoxy-4'-fluorochalcone
• 英文别名: 3-(4-fluorophenyl)-1-(2-hydroxy-4,6-dimethoxyphenyl)prop-2-en-1-one
• CAS: 720676-01-7
• 化学式: C₁₇H₁₅FO₄
• 分子量: 302.302
• InChiKey: WZCYSJXPWSPCHO-UHFFFAOYSA-N

物化性质

• 熔点：
  139-141 °C
• 沸点：
  502.8±50.0 °C(Predicted)
• 密度：
  1.257±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-hydroxy-4,6-dimethoxy-4'-fluorochalcone 在 双氧水 作用下， 以 水 为溶剂， 反应 24.0h， 以189 mg的产率得到(2Z)-2-(4-fluorobenzylidene)-4,6-dimethoxy-1-benzofuran-3(2H)-one
  参考文献：
  名称：

  A One-Pot Synthesis of Aurones from Substituted Acetophenones and Benz­aldehydes: A Concise Synthesis of Aureusidin

  摘要：

  A one-pot synthesis of aurones from substituted acetophenone and benzaldehyde has been developed on the basis of an improved Algar-Flynn-Oyamada reaction. By using this method, several aurones were prepared in three steps from commercial starting materials. The usefulness of this one-pot strategy was confirmed by a synthesis of aureusidin, an inhibitor of iodothyronine deiodinase, in 41% overall yield. In comparison with a two-step synthesis of this product from the same substrates, the one-pot strategy was more effective, giving a higher yield and requiring fewer and simpler operations.

  DOI：

  10.1055/s-0031-1291153
• 作为产物：
  描述：

  2,4,6-三羟基苯乙酮一水合物 在 potassium carbonate 、 potassium hydroxide 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 4.0h， 生成 2-hydroxy-4,6-dimethoxy-4'-fluorochalcone
  参考文献：
  名称：

  具有类黄酮支架的选择性强效 CDK9 抑制剂的设计和优化，用于治疗急性髓系白血病

  摘要：

  急性髓系白血病（AML）是一种常见的血液肿瘤，发病率和死亡率很高。CDK9 作为关键转录调节因子，通过 RNA 聚合酶 II 的磷酸化促进转录延伸，进一步控制 Mcl-1 和 c-Myc 的蛋白质水平。因此，CDK9被认为是AML治疗的一个有前景的治疗靶点。在这里，我们介绍了带有类黄酮支架的 CDK9 抑制剂的设计、合成和评估。其中，化合物21a成为一种高选择性CDK9抑制剂（IC 50  = 6.7 nM），对大多数其他CDK家族成员表现出超过80倍的选择性和高激酶选择性。在 Mv4-11 细胞中，21a有效阻碍细胞增殖 (IC 50  = 60 nM)，并通过下调 Mcl-1 和 c-Myc 诱导细胞凋亡。值得注意的是，21a在 Mv4-11 异种移植肿瘤模型中表现出对肿瘤生长的显着抑制作用。这些发现表明化合物21a有希望成为治疗 AML 的潜在候选药物。

  DOI：

  10.1016/j.ejmech.2023.115711

文献信息

• Attrition-Enhanced Deracemization and Absolute Asymmetric Synthesis of Flavanones from Prochiral Precursors
  作者：Waku Shimizu、Naohiro Uemura、Yasushi Yoshida、Takashi Mino、Yoshio Kasashima、Masami Sakamoto

  DOI：10.1021/acs.cgd.0c00955

  日期：2020.9.2

  Seven racemic 5,7-dimethoxyflavanones afforded conglomerate crystals upon recrystallization from a solvent. Three methodologies were investigated to achieve asymmetric transformation based on dynamic crystallization of the chiral conglomerate system. The first was chiral symmetry breaking of racemic flavanones by attrition-enhanced deracemization. Continuous suspension of racemic flavanones in a small

  从溶剂中重结晶后，七个外消旋的5,7-二甲氧基黄酮酮提供了凝聚物晶体。研究了三种方法来实现基于手性团聚体系统动态结晶的不对称转化。第一个是通过减磨增强的去消旋作用使外消旋黄烷酮手性对称性破坏。在碱（1,8-二氮杂双环[5.4.0]十一碳-7-烯（DBU））和玻璃珠存在下，外消旋黄烷酮在少量丙醇中的连续悬浮促进了手性对称性的破坏并将黄烷酮转化为晶体具有78％至99％ee的（+）-或（-）-对映体。第二种方法涉及中间体醛醇缩合产物的环化，以产生具有90％ee的旋光性黄烷酮，其中涉及可逆的oxa-Michael加成反应以及减磨作用。
• Synthesis of Ochnaflavone and Its Inhibitory Activity on PGE₂Production
  作者：Sung Soo Kim、Van Anh Vo、Haeil Park

  DOI：10.5012/bkcs.2014.35.11.3219

  日期：2014.11.20

  the contrary, the inhibition mechanism of wogonin was somewhat different from that of ochnaflavone although wogonin, a natural occurring anti-inflammatory flavonoid, showed strong inhibitory activity of production (), and seems to be COX-2 enzyme inhibition. Our concise total synthesis of ochnaflavone enable us to provide sufficient quantities of material for advanced biological studies as well as to

  Ochnaflavone 是一种天然存在的双黄酮类化合物，由通过 COC 键连接的两个芹菜素（5,7,4'-三羟基黄酮）单元组成，首先合成并评估了其对生产的抑制活性。通过改性乌尔曼二芳基醚形成作为关键步骤完成全合成。在不同的反应条件下探索了 4'-卤代黄酮和 3'-羟基-5,7,4'-三甲氧基黄酮的偶联反应。4'-氟-5,7-二甲氧基黄酮 (2c) 和 3'-羟基-5,7,4'-三甲氧基黄酮 (2d) 在 N,N-二甲基乙酰胺中的反应以 58% 的收率得到偶联化合物 3。合成的 ochnaflavone 强烈抑制 LPS 激活的 RAW 264.7 细胞中 PGE2 的产生 ()，这是由于 COX-2 的表达减少。相反，汉黄芩素的抑制机制与茯苓黄酮有些不同，虽然汉黄芩素是一种天然存在的抗炎黄酮类化合物，具有很强的抑制活性，似乎是对COX-2酶的抑制。我们简洁的 ochnaflavone 全
• 苯并吡喃酮类化合物、药物组合物和应用
  申请人：中国药科大学

  公开号：CN115160279A

  公开（公告）日：2022-10-11

  本发明公开了一种苯并吡喃酮类化合物、药物组合物和应用，该化合物结构如式I，还包含其药学上可接受的盐。该类化合物及其药物组合物可有效抑制cGAs活性，抑制活性最优低于5μM浓度水平。其制备的为cGAS抑制剂药物，应用广泛，可用于治疗自身免疫性疾病、炎症性疾病或神经变性病症，在分子水平和细胞水平均可以发挥药效，并且该类化合物制备方法适用性广，简便易行。
• Structure−Activity Relationship Studies of Chalcone Leading to 3-Hydroxy-4,3′,4′,5′-tetramethoxychalcone and Its Analogues as Potent Nuclear Factor κB Inhibitors and Their Anticancer Activities
  作者：Balasubramanian Srinivasan、Thomas E. Johnson、Rahul Lad、Chengguo Xing

  DOI：10.1021/jm901278z

  日期：2009.11.26

  Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-kappa B) activation. The structures of chalcone-based NF-kappa B inhibitors vary significantly that there is minimum information about their structure-activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-kappa B inhibition, to explore the feasibility of developing simple chalcone-based potent NF-kappa B inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-kappa B inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-kappa B inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-kappa B inhibitory activities, suggesting that suppressing NF-kappa B activation is likely responsible for at least some of the cytotoxicities. One lead compound effectively inhibits lung tumor growth with no signs of adverse side effects.
• Collateral sensitivity of resistant MRP1-overexpressing cells to flavonoids and derivatives through GSH efflux
  作者：Doriane Lorendeau、Lauriane Dury、Estelle Genoux-Bastide、Florine Lecerf-Schmidt、Claudia Simões-Pires、Pierre-Alain Carrupt、Raphaël Terreux、Sandrine Magnard、Attilio Di Pietro、Ahcène Boumendjel、Hélène Baubichon-Cortay

  DOI：10.1016/j.bcp.2014.05.017

  日期：2014.8

  The multidrug resistance protein 1 (MRP1) is involved in multidrug resistance of cancer cells by mediating drug efflux out of cells, often in co-transport with glutathione (GSH). GSH efflux mediated by MRP1 can be stimulated by verapamil. In cells overexpressing MRP1, we have previously shown that verapamil induced a huge intracellular GSH depletion which triggered apoptosis of the cells. That phenomenon takes place in the more global anticancer strategy called "collateral sensitivity" and could be exploited to eradicate some chemoresistant cancer cells. Seeking alternative compounds to verapamil, we screened a library of natural flavonoids and synthetic derivatives. A large number of these compounds stimulate MRP1-mediated GSH efflux and the most active ones have been evaluated for their cytotoxic effect on MRP1-overexpressing cells versus parental cells. Interestingly, some are highly and selectively cytotoxic for MRP1-cells, leading them to apoptosis. However, some others do not exhibit any cytotoxicity while promoting a strong GSH efflux, indicating that GSH efflux is necessary but not sufficient for MRP1-cells apoptosis. In support to this hypothesis, structure activity relationships show that the absence of a hydroxyl group at position 3 of the flavonoid C ring is an absolute requirement for induction of MRP1-cells death, but is not for GSH efflux stimulation. Chrysin (compound 8) and its derivatives, compounds 11 and 22, exhibit a high selectivity toward MRP1-cells with a IC50 value of 4.1 mu M for compound 11 and 4.9 mu M for chrysin and compound 22, making them among the best described selective killer compounds of multidrug ABC transporter-overexpressing cells. (C) 2014 Elsevier Inc. All rights reserved.