(E)-1-(3'-fluoro-[1,1'-biphenyl]-2-yl)-3-(3-hydroxy-4-methoxyphenyl)prop-2-en-1-one

• 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: (E)-1-(3'-fluoro-[1,1'-biphenyl]-2-yl)-3-(3-hydroxy-4-methoxyphenyl)prop-2-en-1-one
• 英文别名: (E)-1-[2-(3-fluorophenyl)phenyl]-3-(3-hydroxy-4-methoxyphenyl)prop-2-en-1-one
• 化学式: C₂₂H₁₇FO₃
• 分子量: 348.374
• InChiKey: PWLSGAPPAPJBGG-PKNBQFBNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-1-(3'-fluoro-[1,1'-biphenyl]-2-yl)-3-(3-hydroxy-4-methoxyphenyl)prop-2-en-1-one 在 羟胺 、 potassium carbonate 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 15.0h， 生成 (E)-4-(5-(3-(3′-fluoro-[1,1′-biphenyl]-2-yl)-3-oxoprop-1-en-1-yl)-2-methoxyphenoxy)-N-hydroxybutanamide
  参考文献：
  名称：

  Discovery of a 2,6-diarylpyridine-based hydroxamic acid derivative as novel histone deacetylase 8 and tubulin dual inhibitor for the treatment of neuroblastoma

  摘要：

  DOI：

  10.1016/j.bioorg.2022.106112
• 作为产物：
  描述：

  异香兰素 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium carbonate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 0.33h， 生成 (E)-1-(3'-fluoro-[1,1'-biphenyl]-2-yl)-3-(3-hydroxy-4-methoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  Discovery of Potent Cytotoxic Ortho-Aryl Chalcones as New Scaffold Targeting Tubulin and Mitosis with Affinity-Based Fluorescence

  摘要：

  A series of new ortho-aryl chalcones have been designed and synthesized. Many of these compounds were found to exhibit significant antiproliferation activity toward a panel of cancer cell lines. Selected compounds show potent cytotoxicity against several drug resistant cell lines including paclitaxel (Taxol) resistant human ovarian carcinoma cells, vincristine resistant human ileocecum carcinoma cells, and doxorubicin resistant human breast carcinoma cells. Further investigation revealed that active analogues could inhibit the microtubule polymerization by binding to colchicine site and thus induce multipolar mitosis, G2/M phase arrest, and apoptosis of cancer cells. Furthermore, affinity-based fluorescence enhancement was observed during the binding of active compounds with tubulin, which greatly facilitated the determination of tubulin binding site of the compounds. Finally, selected compound 26 was found to exhibit obvious in vivo antitumor activity in A549 tumor xenografts model. Our systematic studies implied a new scaffold targeting tubulin and mitosis for novel antitumor drug discovery.

  DOI：

  10.1021/jm500024v

文献信息

• O-Phenyl Chalcone Compounds And Preparation Method And Use Thereof
  申请人：Sun Yat-Sen University

  公开号：US20160333033A1

  公开（公告）日：2016-11-17

  Disclosed are an o-phenyl chalcone compounds and preparation methods and uses thereof. The o-phenyl chalcone compounds are capable of inhibiting the aggregation of microtubules in tumor cells and influencing the mitosis of the cells, and have a high antitumor activity. The compounds also have inhibitory activity against proliferation on various tumor cells, such as a human ovary cancer cell A2780, a human colon cancer cell HCT8, a human breast cancer cell MCF7, a human lung cancer cell A549, a human colon cancer cell SW480, a human nasopharyngeal carcinoma cell CNE2, a human liver cancer cell HepG2 and the like at nanomole concentrations.

  揭示了一种 o-苯基查尔酮化合物及其制备方法和用途。这些 o-苯基查尔酮化合物能够抑制肿瘤细胞微管的聚集，影响细胞的有丝分裂，并具有较高的抗肿瘤活性。这些化合物还在纳摩尔浓度下对各种肿瘤细胞的增殖具有抑制活性，如人卵巢癌细胞A2780、人结肠癌细胞HCT8、人乳腺癌细胞MCF7、人肺癌细胞A549、人结肠癌细胞SW480、人鼻咽癌细胞CNE2、人肝癌细胞HepG2等。
• O-PHENYL CHALCONE COMPOUND AND PREPARATION METHOD AND USE THEREOF
  申请人：Sun Yat-Sen University

  公开号：EP3118204A1

  公开（公告）日：2017-01-18

  Disclosed are an o-phenyl chalcone compounds and preparation methods and uses thereof. The o-phenyl chalcone compounds are capable of inhibiting the aggregation of microtubules in tumor cells and influencing the mitosis of the cells, and has a high antitumor activity. The compounds also have inhibitory activity against proliferation on various tumor cells, such as a human ovary cancer cell A2780, a human colon cancer cell HCT8, a human breast cancer cell MCF7, a human lung cancer cell A549, a human colon cancer cell SW480, a human nasopharyngeal carcinoma cell CNE2, a human liver cancer cell HepG2 and the like at nanomole concentrations.

  本发明公开了一种邻苯基查尔酮化合物及其制备方法和用途。邻苯基查尔酮化合物能够抑制肿瘤细胞中微管的聚集，影响细胞的有丝分裂，具有很高的抗肿瘤活性。这些化合物还具有抑制各种肿瘤细胞增殖的活性，如纳摩尔浓度下的人卵巢癌细胞 A2780、人结肠癌细胞 HCT8、人乳腺癌细胞 MCF7、人肺癌细胞 A549、人结肠癌细胞 SW480、人鼻咽癌细胞 CNE2、人肝癌细胞 HepG2 等。
• Discovery of Potent Cytotoxic Ortho-Aryl Chalcones as New Scaffold Targeting Tubulin and Mitosis with Affinity-Based Fluorescence
  作者：Cuige Zhu、Yinglin Zuo、Ruimin Wang、Baoxia Liang、Xin Yue、Gesi Wen、Nana Shang、Lei Huang、Yu Chen、Jun Du、Xianzhang Bu

  DOI：10.1021/jm500024v

  日期：2014.8.14

  A series of new ortho-aryl chalcones have been designed and synthesized. Many of these compounds were found to exhibit significant antiproliferation activity toward a panel of cancer cell lines. Selected compounds show potent cytotoxicity against several drug resistant cell lines including paclitaxel (Taxol) resistant human ovarian carcinoma cells, vincristine resistant human ileocecum carcinoma cells, and doxorubicin resistant human breast carcinoma cells. Further investigation revealed that active analogues could inhibit the microtubule polymerization by binding to colchicine site and thus induce multipolar mitosis, G2/M phase arrest, and apoptosis of cancer cells. Furthermore, affinity-based fluorescence enhancement was observed during the binding of active compounds with tubulin, which greatly facilitated the determination of tubulin binding site of the compounds. Finally, selected compound 26 was found to exhibit obvious in vivo antitumor activity in A549 tumor xenografts model. Our systematic studies implied a new scaffold targeting tubulin and mitosis for novel antitumor drug discovery.
• Synthesis and evaluation of anticancer activity of BOC26P, an ortho-aryl chalcone sodium phosphate as water-soluble prodrugs in vitro and in vivo
  作者：Cuige Zhu、Ruimin Wang、Weichao Zheng、Daoyuan Chen、Xin Yue、Yingnan Cao、Wenjing Qin、Haixia Sun、Youqiao Wang、Ziyi Liu、Baojian Li、Jun Du、Xianzhang Bu、Binhua Zhou

  DOI：10.1016/j.biopha.2017.10.006

  日期：2017.12

  Major limitations of chalcones as clinical anticancer agents are water insolubility and poor bioavailability, which may be improved by a classic phosphate prodrug strategy that targets non-specific alkaline phosphatase (ALP) for releasing the parent drug in vivo. In this study, we found that BOC26P, a phosphate prodrug of chalcone OC26, exhibits excellent water solubility and improved plasma concentration in vivo by either i.v. or p.o. compared with the parent drug. In pace with decreased inhibitory activity of BOC26P against microtubule polymerization in vitro and in cells, the antiproliferative activity of BOC26P is attenuated in A549 and HLF cells. However, the antitumor effect of BOC26P increases in an A549 xenograft model as compared to the equimolar concentration of OC26, suggesting that complex tumor microenvironment would be another important influence factor to regulate the antitumor activity of BOC26P in vivo. In conclusion, these observations showed that the traditional phosphate prodrug strategy would be a promising and easy method to increase water solubility and anticancer activity of chalcones for the clinical developments of anticancer agents.
• O-PHENYL CHALCONE COMPOUNDS AND USES THEREOF
  申请人：Sun Yat-Sen University

  公开号：US20170247398A1

  公开（公告）日：2017-08-31

  Disclosed are an o-phenyl chalcone compounds and preparation methods and uses thereof. The o-phenyl chalcone compounds are capable of inhibiting the aggregation of microtubules in tumor cells and influencing the mitosis of the cells, and has a high antitumor activity. The compounds also have inhibitory activity against proliferation on various tumor cells, such as a human ovary cancer cell A2780, a human colon cancer cell HCT8, a human breast cancer cell MCF7, a human lung cancer cell A549, a human colon cancer cell SW480, a human nasopharyngeal carcinoma cell CNE2, a human liver cancer cell HepG2 and the like at nanomole concentrations.