4,4'-bis(tetrahydropyran-2-yloxy)chalcone | 457629-77-5

• 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: 4,4'-bis(tetrahydropyran-2-yloxy)chalcone
• 英文别名: 1,3-Bis{4-[(oxan-2-yl)oxy]phenyl}prop-2-en-1-one；1,3-bis[4-(oxan-2-yloxy)phenyl]prop-2-en-1-one
• CAS: 457629-77-5
• 化学式: C₂₅H₂₈O₅
• 分子量: 408.494
• InChiKey: JZFBILQPWCCABQ-UHFFFAOYSA-N

物化性质

• 沸点：
  606.3±55.0 °C(Predicted)
• 密度：
  1.184±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4,4'-bis(tetrahydropyran-2-yloxy)chalcone 在 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 4',4-dihydroxychalcone
  参考文献：
  名称：

  Chalcones and Chalcone-mimetic Derivatives as Notch Inhibitors in a Model of T-cell Acute Lymphoblastic Leukemia

  摘要：

  Based on hit-likeness and chemical diversity, a number of chalcones and chalcone-mimetic compounds were selected as putative Notch inhibitors. The evaluation of the antiproliferative effect combined with the inhibition of Notchl expression in KOPTK1 cell line identified compound 18, featuring a tetrahydronaphthalene-based scaffold, as a new promising Notch-blocking agent.

  DOI：

  10.1021/acsmedchemlett.8b00608
• 作为产物：
  描述：

  对羟基苯甲醛 在 4-甲基苯磺酸吡啶 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 4,4'-bis(tetrahydropyran-2-yloxy)chalcone
  参考文献：
  名称：

  Functionalized curcumin analogs as potent modulators of the Wnt/β-catenin signaling pathway

  摘要：

  Osteosarcoma is a primary bone malignancy with aggressive metastatic potential and poor prognosis rates. In our earlier work we have investigated the therapeutic potential of curcumin as an anti-invasive agent in osteosarcoma by its ability to regulate the Wnt/beta-catenin signaling pathway. However, the clinical use of curcumin is limited owing to its low potency and poor pharmacokinetic profile. In this study, an attempt was made to achieve more potent Wnt inhibitory activity in osteosarcoma cells by carrying out synthetic chemical modifications of curcumin. We synthesized a total of five series consisting of 43 curcumin analogs and screened in HEK293T cells for inhibition of beta-catenin transcriptional activity. Six promising analogs, which were 6.5- to 60-fold more potent than curcumin in inhibiting Wnt activity, were further assessed for their anti-invasive activity and Wnt inhibitory mechanisms. Western blot analysis showed disruption of beta-catenin protein nuclear translocation following treatment with analogs 2f, 3c and 4f. Using transwell assays, we also found that these compounds were more potent than la (curcumin) in impeding the invasion of osteosarcoma cells, possibly through suppressing MMP-9 activity. Structure-activity-relationship studies revealed that Wnt inhibitory effects could be enhanced by shortening and restraining the flexibility of the 7-carbon linker moiety connecting the terminal aromatic rings of curcumin and substituting both rings with appropriate substituents. Our results demonstrate that the synthesized curcumin analogs are more potent Wnt inhibitors in osteosarcoma cell lines as compared to parental curcumin and are good lead compounds for further development. Future in vivo tests with these compounds will define their therapeutic potentials as promising drug candidates for clinical treatment of osteosarcoma. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.10.073

文献信息

• Aminopyridine derivatives as estrogen receptor modulators
  申请人：——

  公开号：US20040152688A1

  公开（公告）日：2004-08-05

  Aminopyridine derivatives of the following formula I which exhibit pharmacological activity at estrogen receptors alpha (ER&agr;) and beta (ER&bgr;) are described herein. The described invention also includes compositions and medicaments containing the aminopyridine derivatives as well as processes for the preparation and use of such compounds, compositions and medicaments.

  本文描述了在雌激素受体α（ER&agr;）和β（ER&bgr;）上表现出药理活性的下式I的氨基吡啶衍生物。所述发明还包括含有氨基吡啶衍生物的组合物和药物，以及制备和使用此类化合物、组合物和药物的工艺。
• Synthesis and topoisomerase II inhibitory and cytotoxic activity of oxiranylmethoxy- and thiiranylmethoxy-chalcone derivatives
  作者：Younghwa Na、Jung-Min Nam

  DOI：10.1016/j.bmcl.2010.11.037

  日期：2011.1

  In order to find potential anticancer drug candidate targeting topoisomerases enzyme, we have designed and synthesized oxiranylmethoxy- and thiiranylmethoxy-retrochalcone derivatives and evaluated their pharmacological activity including topoisomerases inhibitory and cytotoxic activity. Of the compounds prepared compound 25 showed comparable or better cytotoxic activity against cancer cell lines tested. Compound 25 inhibited MCF7 (IC50: 0.49 +/- 0.21 mu M) and HCT15 (IC50: 0.23 +/- 0.02 mu M) carcinoma cell growth more efficiently than references. In the topoisomerases inhibition test, all the compounds were inactive to topoisomerase I but moderate inhibitors to topoisomerase II enzyme. Especially, compound 25 inhibited topoisomerase II activity with comparable extent to etoposide at 100 mu M concentrations. Correlation between cytotoxicity and topoisomerase II inhibitory activity implies that compound 25 can be a possible lead compound for anticancer drug impeding the topoisomerase II function. (C) 2010 Elsevier Ltd. All rights reserved.
• US7276523B2
  申请人：——

  公开号：US7276523B2

  公开（公告）日：2007-10-02
• Chalcones and Chalcone-mimetic Derivatives as Notch Inhibitors in a Model of T-cell Acute Lymphoblastic Leukemia
  作者：Deborah Quaglio、Nadezda Zhdanovskaya、Gloria Tobajas、Viviana Cuartas、Silvia Balducci、Michael S. Christodoulou、Giancarlo Fabrizi、Marta Gargantilla、Eva-María Priego、Álvaro Carmona Pestaña、Daniele Passarella、Isabella Screpanti、Bruno Botta、Rocco Palermo、Mattia Mori、Francesca Ghirga、María-Jesús Pérez-Pérez

  DOI：10.1021/acsmedchemlett.8b00608

  日期：2019.4.11

  Based on hit-likeness and chemical diversity, a number of chalcones and chalcone-mimetic compounds were selected as putative Notch inhibitors. The evaluation of the antiproliferative effect combined with the inhibition of Notchl expression in KOPTK1 cell line identified compound 18, featuring a tetrahydronaphthalene-based scaffold, as a new promising Notch-blocking agent.
• Functionalized curcumin analogs as potent modulators of the Wnt/β-catenin signaling pathway
  作者：Pay-Chin Leow、Priti Bahety、Choon Pei Boon、Chong Yew Lee、Kheng Lin Tan、Tianming Yang、Pui-Lai Rachel Ee

  DOI：10.1016/j.ejmech.2013.10.073

  日期：2014.1

  Osteosarcoma is a primary bone malignancy with aggressive metastatic potential and poor prognosis rates. In our earlier work we have investigated the therapeutic potential of curcumin as an anti-invasive agent in osteosarcoma by its ability to regulate the Wnt/beta-catenin signaling pathway. However, the clinical use of curcumin is limited owing to its low potency and poor pharmacokinetic profile. In this study, an attempt was made to achieve more potent Wnt inhibitory activity in osteosarcoma cells by carrying out synthetic chemical modifications of curcumin. We synthesized a total of five series consisting of 43 curcumin analogs and screened in HEK293T cells for inhibition of beta-catenin transcriptional activity. Six promising analogs, which were 6.5- to 60-fold more potent than curcumin in inhibiting Wnt activity, were further assessed for their anti-invasive activity and Wnt inhibitory mechanisms. Western blot analysis showed disruption of beta-catenin protein nuclear translocation following treatment with analogs 2f, 3c and 4f. Using transwell assays, we also found that these compounds were more potent than la (curcumin) in impeding the invasion of osteosarcoma cells, possibly through suppressing MMP-9 activity. Structure-activity-relationship studies revealed that Wnt inhibitory effects could be enhanced by shortening and restraining the flexibility of the 7-carbon linker moiety connecting the terminal aromatic rings of curcumin and substituting both rings with appropriate substituents. Our results demonstrate that the synthesized curcumin analogs are more potent Wnt inhibitors in osteosarcoma cell lines as compared to parental curcumin and are good lead compounds for further development. Future in vivo tests with these compounds will define their therapeutic potentials as promising drug candidates for clinical treatment of osteosarcoma. (C) 2013 Elsevier Masson SAS. All rights reserved.