(E,E)-4,6-bis(3,4-dimethoxystyryl)-2-hydroxyl-pyrimidine | 1354972-75-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: (E,E)-4,6-bis(3,4-dimethoxystyryl)-2-hydroxyl-pyrimidine
• 英文别名: 4,6-bis[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-1H-pyrimidin-2-one
• CAS: 1354972-75-0
• 化学式: C₂₄H₂₄N₂O₅
• 分子量: 420.465
• InChiKey: LMXFBXYZWSTWRA-NXZHAISVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  78.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E,E)-4,6-bis(3,4-dimethoxystyryl)-2-hydroxyl-pyrimidine 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 24.0h， 生成 (E,E)-2-(4-(4,6-bis(3,4-dimethoxystyryl)pyrimidin-2-yloxy)-butyl)-1,1,3,3-tetramethylisothiouronium hydrobromide
  参考文献：
  名称：

  Isothiouronium modification empowers pyrimidine-substituted curcumin analogs potent cytotoxicity and Golgi localization

  摘要：

  Most of protein post-translational modifications occur in the Golgi and many human diseases are associated with abnormal Golgi function or improper post translational modifications of proteins in the Golgi. In this study, we designed and synthesized 4 x 6 series of novel isothiouronium-modified (E,E)-4,6-bis(styryl)-pyrimidine analogs and found that they localized at the Golgi as visualized by the intrinsic fluorescence of the analogs. The isothiouronium-modified analogs had potent cytotoxicity in both normal (Chinese Hamster Ovary or CHO) and cancer cells. Furthermore, permethylated isothiouronium-modified analogs showed cancer cell-selective cytotoxicity. The molecular mechanisms underlying Golgi localization of isothiouronium-modified compounds were investigated using 7 CHO and 4 human cancer cell lines and the results indicated that the compounds had binding partners in the Golgi. Thus, isothiouronium-modified analogs might be promising anticancer agents, novel Golgi staining reagents, and useful research tools for studying Golgi functions in normal or cancer cells and in Golgi-related human diseases. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.07.071
• 作为产物：
  描述：

  4,6-二甲基-2-羟基嘧啶盐酸盐 、 3,4-二甲氧基苯甲醛 在 盐酸 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 以70%的产率得到(E,E)-4,6-bis(3,4-dimethoxystyryl)-2-hydroxyl-pyrimidine
  参考文献：
  名称：

  Exploring pyrimidine-substituted curcumin analogues: Design, synthesis and effects on EGFR signaling

  摘要：

  Epidermal growth factor receptor (EGFR) is an effective molecular target of anti-cancer therapies. Curcumin inhibits cancer cell growth in vitro by suppressing gene expression of EGFR and reduces tumor growth in various animal models. To overcome instable and insoluble properties of curcumin as therapeutics, we designed and synthesized six novel pyrimidine-substituted curcumin analogues with or without a hydroxyl group originally present in curcumin. The cell viability tests indicated that IC50 of the analogues containing hydroxyl group were 3 to 8-fold lower than those of the analogues without hydroxyl group in two colon cancer cell lines tested. Western blot analysis indicates the analogues containing hydroxyl group inhibited expression and tyrosine phosphorylation of EGFR. Further protein analyses showed that the analogues had anti-cellular proliferation, pro-apoptosis, and cell cycle arrest properties associated with suppressed EGFR expression. These results indicate that the hydroxyl groups in curcumin and the analogues were critical for observed biological activities. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.053

文献信息

• Guanidine modifications enhance the anti‐herpes simplex virus activity of ( <i>E</i> , <i>E</i> )‐4,6‐bis(styryl)‐pyrimidine derivatives in vitro and in vivo
  作者：Wei Wang、Cuijing Xu、Jianqiang Zhang、Jinpeng Wang、Rilei Yu、Dongping Wang、Ruijuan Yin、Wenmiao Li、Tao Jiang

  DOI：10.1111/bph.14918

  日期：2020.4

  Background and PurposeThe worldwide prevalence of herpes simplex virus (HSV) and shortage of efficient therapeutic strategies to counteract it are global concerns. In terms of treatment, the widely utilized anti‐HSV drugs such as acyclovir have serious limitations, for example, drug resistance and side effects. Here, we have identified the guanidine‐modified (E,E)‐4,6‐bis(styryl)‐pyrimidine (BS‐pyrimidine) derivative compound 5d as an inhibitor of HSV and further elucidated the anti‐HSV mechanisms of compound 5d both in vitro and in vivo.Experimental ApproachCytopathic effect inhibition assay, plaque assay, and immunofluorescence assay were used to evaluate the anti‐HSV effects of compound 5d in vitro. Membrane fusion assays, immunofluorescence assays, Western blotting assays, and pull‐down assays were used to explore the anti‐HSV mechanisms of compound 5d. HSV‐1‐infected mice, combined with haematoxylin–eosin staining and quantitative RT‐PCR, were used to study the anti‐HSV effects of compound 5d in vivo.Key ResultsThe guanidine‐modified compound 5d rather than the un‐modified compound 3a effectively inhibited both HSV‐1 and HSV‐2 multiplication in different cell lines, more effectively than acyclovir. Compound 5d may block virus binding and post‐binding processes such as membrane fusion, by targeting virus gB protein. In addition, compound 5d may also down‐regulate the cellular PI3K/Akt signalling pathway to interfere with HSV replication. Treatment with compound 5d also markedly improved survival and decreased viral titres in HSV‐infected mice.Conclusions and ImplicationsThus, the guanidine‐modified BS‐pyrimidine derivatives have the potential to be developed into novel anti‐HSV agents targeting both virus gB protein and cellular PI3K/Akt signalling pathways.
• Synthesis of a Novel Series of (<i>E</i>,<i>E</i>)-4,6-bis(styryl)-2-<i>O</i>-Glucopyranosyl-Pyrimidines and Their Potent Multidrug Resistance (MDR) Reversal Activity Against Cancer Cells
  作者：Lei Gao、Qian Liu、Sumei Ren、Shengbiao Wan、Tao Jiang、Iris L. K. Wong、Larry M. C. Chow、Shixi Wang

  DOI：10.1080/07328303.2012.689041

  日期：2012.10

  A novel series of methoxy or benzyloxy substituted (E,E)-4,6-bis(styryl)-2-O-glucopyranosyl-pyrimidines as curcuminoid analogs were synthesized in four steps with total yields of 21.5% to 33.9%. A549 and HL60 cells were employed for the anticancer activity testing. The results demonstrated that 5a, 5c, and 5e have some inhibitory activity against the HL-60 cell line. Unfortunately, no compound displayed inhibitory activity against A549 except for 5c. MDR reversal activity results demonstrated that compounds 4a (RF = 12.3) and 4b (RF = 18.5) showed strong reversal activity to the P-gp-mediated LCC6MDR cells compared to verapamil (RF = 3.2) and no cytotoxicity to cancer or normal cell lines even at a high concentrations (100 mu M).