2',4'-dihydroxy-2-methoxylchalcone | 108051-21-4

• 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',4'-dihydroxy-2-methoxylchalcone
• 英文别名: 2',4'-dihydroxy-2-methoxychalcone；2',4'-dihydroxy-2-methoxychalcon；1-(2,4-dihydroxyphenyl)-3-(2-methoxyphenyl)prop-2-en-1-one
• CAS: 108051-21-4
• 化学式: C₁₆H₁₄O₄
• 分子量: 270.285
• InChiKey: ODLVGCCGMXGMGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2',4'-dihydroxy-2-methoxylchalcone 在 palladium on activated charcoal 、 氢气 作用下， 以 四氢呋喃 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 16.0h， 生成 1-(2,4-dihydroxy-phenyl)-3-(2-methoxy-phenyl)-propan-1-one
  参考文献：
  名称：

  New homoisoflavonoid analogues protect cells by regulating autophagy

  摘要：

  As a special group of naturally occurring flavonoids, homoisoflavonoids have been discovered as active components of several traditional Chinese medicines for nourishing heart and mind. In this study, twenty homoisoflavonoid analogues, including different substitution groups on rings A and B, as well as heteroaromatic B ring, were synthesized and evaluated for their cardioprotective and neuroprotective activities. In a H2O2-induced H9c2 cardiomyocytes injury assay, nine homoisoflavonoid analogues showed promising activities in the same level as the positive control, diazoxide. Six cardioprotective compounds with representative structure diversities were then evaluated for their neuroprotective effects on MPP+ induced SH-SY5Y cell injury model. Furthermore, autophagy inducing monodansylcadaverine (MDC) fluorescence staining methods and molecular docking studies indicated the action mechanism of these compounds may involve autophagy regulating via class I P13K signaling pathway. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.01.086
• 作为产物：
  描述：

  1-[2-羟基-4-(甲氧基甲氧基)苯基]乙酮 在 盐酸 、 potassium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 生成 2',4'-dihydroxy-2-methoxylchalcone
  参考文献：
  名称：

  Synthesis and biological evaluations of chalcones, flavones and chromenes as farnesoid x receptor (FXR) antagonists

  摘要：

  Farnesoid X receptor (FXR), a nuclear receptor mainly distributed in liver and intestine, has been regarded as a potential target for the treatment of various metabolic diseases, cancer and infectious diseases related to liver. Starting from two previously identified chalcone-based FXR antagonists, we tried to increase the activity through the design and synthesis of a library containing chalcones, flavones and chromenes, based on substitution manipulation and conformation (ring closure) restriction strategy. Many chalcones and four chromenes were identified as microM potent FXR antagonists, among which chromene 11c significantly decreased the plasma and hepatic triglyceride level in KKay mice. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.02.037

文献信息

• 7-Hydroxy-benzopyran-4-one Derivatives: A Novel Pharmacophore of Peroxisome Proliferator-Activated Receptor α and -γ (PPARα and γ) Dual Agonists
  作者：Azadeh Matin、Navnath Gavande、Moon S. Kim、Nancy X. Yang、Noeris K. Salam、Jane R. Hanrahan、Rebecca H. Roubin、David E. Hibbs

  DOI：10.1021/jm900964r

  日期：2009.11.12

  Design, synthesis, and in vitro bioevaluation of a new class of potential dual PPARα and γ agonists discovered through a structure-driven design paradigm are described. The 7-hydroxy-benzopyran-4-one moiety (includes flavones, flavanones, and isoflavones) is the key pharmacophore of these novel molecules, exhibiting similarity to the core structure of both fibrates and thiazolidinediones. New lead

  描述了通过结构驱动设计范式发现的新型潜在的双重PPARα和γ双重激动剂的设计，合成和体外生物评价。7-羟基-苯并吡喃-4-酮部分（包括黄酮，黄烷酮和异黄酮）是这些新分子的关键药效​​基团，与贝特类药物和噻唑烷二酮的核心结构相似。从“保健食品”和合成类似物中鉴定出新的PPAR配体。总共筛选了77个分子，包括查耳酮，黄酮，黄烷酮，异黄酮和吡唑衍生物，并进行了双重激动剂的构效关系研究。化合物68，70，72，和76被鉴定为新型有效的PPARα和γ双重激动剂。这些新型分子可能会成为PPAR相关疾病（包括II型糖尿病和代谢综合征）未来的领先者。
• Plasmin Regulation through Allosteric, Sulfated, Small Molecules
  作者：Rami Al-Horani、Rajesh Karuturi、Domonique White、Umesh Desai

  DOI：10.3390/molecules20010608

  日期：——

  matrix remodeling. Heparin, a natural polydisperse sulfated glycosaminoglycan, is known to allosterically modulate plasmin activity. No small allosteric inhibitor of plasmin has been discovered to date. We screened an in-house library of 55 sulfated, small glycosaminoglycan mimetics based on nine distinct scaffolds and varying number and positions of sulfate groups to discover several promising hits. Of

  纤溶酶是一种关键的丝氨酸蛋白酶，在血块溶解和细胞外基质重塑中起主要作用。肝素是一种天然的多分散的硫酸化糖胺聚糖，已知会变构地调节纤溶酶的活性。迄今为止，尚未发现纤溶酶的变构抑制剂。我们基于9个不同的支架以及不同数量和位置的硫酸盐基团，筛选了55个硫酸化的小糖胺聚糖模拟物的内部库，以发现一些有前途的命中。其中，发现五硫酸化的类黄酮-喹唑啉酮二聚体32是最有效的硫酸化纤溶酶小抑制剂（IC50 = 45μM，功效= 100％）。Michaelis-Menten动力学研究表明，这些抑制剂对纤溶酶具有变构抑制作用。研究还表明，最有效的抑制剂对纤溶酶的选择性优于凝血酶和Xa因子，两种丝氨酸蛋白酶在凝血级联反应中 有趣的是，不同的抑制剂表现出不同的功效水平（40％-100％），这一观察结果暗示了变构过程提供的独特优势。总体而言，我们的工作提出了首个小型的合成别构纤溶酶抑制剂，用于进一步的合理设计。
• Structure Modification of FXR Antagonistic Chalcones and Their Inhibitory Effects on NSCLC Cell Proliferation and Metastasis
  作者：Shuaishuai Niu、Guoning Zhang、Na Wang、Guangyao Lv、Jinsong Liu、Hongbo Wang、Wei‐Shuo Fang

  DOI：10.1002/cmdc.202100778

  日期：2022.6.3

  A chalcone derivative 6 p was synthesized and identified as an FXR-selective antagonist, which inhibits non-small-cell lung cancer (NSCLC) cell proliferation and migration in an FXR-dependent manner. It blocks cell cycle in G1 phase and promotes apoptosis. These results demonstrate the potential of this type of FXR antagonist as targeted therapeutics for NSCLC.

  一种查尔酮衍生物 6 p被合成并鉴定为 FXR 选择性拮抗剂，它以 FXR 依赖性方式抑制非小细胞肺癌 (NSCLC) 细胞增殖和迁移。它阻断G 1期的细胞周期并促进细胞凋亡。这些结果证明了这种类型的 FXR 拮抗剂作为 NSCLC 靶向治疗剂的潜力。
• New homoisoflavonoid analogues protect cells by regulating autophagy
  作者：Li-She Gan、Lin-Wei Zeng、Xiang-Rong Li、Chang-Xin Zhou、Jie Li

  DOI：10.1016/j.bmcl.2017.01.086

  日期：2017.3

  As a special group of naturally occurring flavonoids, homoisoflavonoids have been discovered as active components of several traditional Chinese medicines for nourishing heart and mind. In this study, twenty homoisoflavonoid analogues, including different substitution groups on rings A and B, as well as heteroaromatic B ring, were synthesized and evaluated for their cardioprotective and neuroprotective activities. In a H2O2-induced H9c2 cardiomyocytes injury assay, nine homoisoflavonoid analogues showed promising activities in the same level as the positive control, diazoxide. Six cardioprotective compounds with representative structure diversities were then evaluated for their neuroprotective effects on MPP+ induced SH-SY5Y cell injury model. Furthermore, autophagy inducing monodansylcadaverine (MDC) fluorescence staining methods and molecular docking studies indicated the action mechanism of these compounds may involve autophagy regulating via class I P13K signaling pathway. (C) 2017 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluations of chalcones, flavones and chromenes as farnesoid x receptor (FXR) antagonists
  作者：Guoning Zhang、Shuainan Liu、Wenjuan Tan、Ruchi Verma、Yuan Chen、Deyang Sun、Yi Huan、Qian Jiang、Xing Wang、Na Wang、Yang Xu、Chiwai Wong、Zhufang Shen、Ruitang Deng、Jinsong Liu、Yanqiao Zhang、Weishuo Fang

  DOI：10.1016/j.ejmech.2017.02.037

  日期：2017.3

  Farnesoid X receptor (FXR), a nuclear receptor mainly distributed in liver and intestine, has been regarded as a potential target for the treatment of various metabolic diseases, cancer and infectious diseases related to liver. Starting from two previously identified chalcone-based FXR antagonists, we tried to increase the activity through the design and synthesis of a library containing chalcones, flavones and chromenes, based on substitution manipulation and conformation (ring closure) restriction strategy. Many chalcones and four chromenes were identified as microM potent FXR antagonists, among which chromene 11c significantly decreased the plasma and hepatic triglyceride level in KKay mice. (C) 2017 Elsevier Masson SAS. All rights reserved.