(2E,4E)-5-phenyl-1-(3,4,5-trimethoxyphenyl)penta-2,4-dien-1-one | 1082591-53-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2E,4E)-5-phenyl-1-(3,4,5-trimethoxyphenyl)penta-2,4-dien-1-one
• CAS: 1082591-53-4
• 化学式: C₂₀H₂₀O₄
• 分子量: 324.376
• InChiKey: GTURNHNRMXXRNJ-MKICQXMISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2E,4E)-5-phenyl-1-(3,4,5-trimethoxyphenyl)penta-2,4-dien-1-one 在 对甲基苯磺酰甲基异腈 、 sodium hydride 作用下， 以 乙醚 、 二甲基亚砜 、 mineral oil 为溶剂， 反应 4.0h， 以51%的产率得到(E)-(4-styryl-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  Structure-activity relationship studies and in vitro and in vivo anticancer activity of novel 3-aroyl-1,4-diarylpyrroles against solid tumors and hematological malignancies

  摘要：

  Novel 3-aroyl-1,4-diarylpyrrole derivatives were synthesized to explore structure-activity relationships at the phenyls at positions 1 and 4 of the pyrrole. The presence of amino phenyl rings at positions 1 and 4 of the pyrrole ring were found to be a crucial requirement for potent antitumor activity. Several compounds strongly inhibited tubulin assembly through binding to the colchicine site. Compounds 42, 44, 48, 62 and 69 showed antitumor activity with low nanomolar 1050 values in several cancer cell lines. Compound 48 was generally more effective as an inhibitor of glioblastoma, colorectal and urinary bladder cancer cell lines; 69 consistently inhibited CML cell lines and demonstrated superiority in nilotinib and imatinib resistant LAMA84-R and KBM5-T3151 cells. In animal models, compound 48 exhibited significant inhibition of the growth of T24 bladder carcinoma and ES-2 ovarian clear cell carcinoma tumors. Compounds 48 and 69 represent robust lead compounds for the design of new broadspectrum anticancer agents active in different types of solid and hematological tumors. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111828
• 作为产物：
  描述：

  苯甲醛 在 哌啶 、 溶剂黄146 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 (2E,4E)-5-phenyl-1-(3,4,5-trimethoxyphenyl)penta-2,4-dien-1-one
  参考文献：
  名称：

  二芳基戊二烯酮衍生物（姜黄素类似物）：合成和抗炎活性。

  摘要：

  设计并合成了一系列新的（2E，4E）-1-（取代苯基）-5-（取代苯基）戊-2,4-二烯-1-酮衍生物。通过X射线确定化合物3i，3k。已经筛选了所有化合物的抗炎活性，其特征在于评估了它们对LPS刺激的细胞RAW 264.7中LPS诱导的IL-6和TNF-α释放的抑制作用。化合物3i对降低IL-6和TNF-α表现出最高的抗炎活性。进一步的研究表明标题化合物3i抑制了蛋白p-p65，iNOS，COX-2 LPS诱导的表达。免疫荧光法还显示化合物3i可以轻微降低细胞核中的激活p65。这些结果表明化合物3i的抗炎作用可能部分是由于其对NF-κB信号传导途径的抑制作用。

  DOI：

  10.1016/j.bmcl.2017.02.056

文献信息

• Design, synthesis and SARs of novel telomerase inhibitors based on BIBR1532
  作者：Chao Liu、Hua Zhou、Xiao Bao Sheng、Xin Hua Liu、Fei Hu Chen

  DOI：10.1016/j.bioorg.2020.104077

  日期：2020.9

  their telomerase inhibitory activity were tested. Among them, eight compounds showed good activity against cancer cells, among them compounds 56, 57 and 59 also showed low toxicity. Some of them showed excellent telomerase inhibitory activity with IC50 values ranging from 0.62 μM to 8.87 μM. Based on above, in depth structure-activity relationships were summarized, the compounds by replacing methyl group

  端粒酶已成为开发抗肿瘤药物的新的流行靶标之一。根据已进入临床研究阶段的BIBR1532的结构特征，设计并合成了6个系列的64种具有不同结构特征的新化合物。测试了对SGC-7901，MGC-803，SMMC-7721，A375和GES细胞系的抑制活性及其端粒酶抑制活性。其中，8个化合物显示良好的活性针对癌细胞，其中化合物56，57和59还显示出低毒性。其中一些对IC 50表现出优异的端粒酶抑制活性值范围从0.62μM到8.87μM。据此，在深度构效关系上进行了总结，用氰化物取代甲基并保留酰胺部分的化合物具有良好的抗肿瘤活性，中等的细胞毒性和较好的端粒酶抑制活性。该结果应在基于BIBR1532的结构优化中用作进一步开发小分子端粒酶抑制剂的参考。
• VINYLOGOUS CHALCONE DERIVATIVES AND THEIR MEDICAL USE
  申请人：Erker Thomas

  公开号：US20130123367A1

  公开（公告）日：2013-05-16

  The present invention relates to vinylogous chalcone derivatives, in particular the compounds of formula (I) as described and defined herein, pharmaceutical compositions comprising these compounds, and their medical use, including their use in the treatment or prevention of cancer, in particular malignant hematological diseases/disorders.

  本发明涉及乙烯基差位查尔酮衍生物，特别是本文所描述和定义的式(I)化合物，包括含有这些化合物的制药组合物，以及它们在医学上的用途，包括它们在治疗或预防癌症，特别是恶性血液疾病/紊乱方面的用途。
• One-pot synthesis of cinnamylideneacetophenones and their in vitro cytotoxicity in breast cancer cells
  作者：David J. Weldon、Marilyn D. Saulsbury、Joshua Goh、Leah Rowland、Petreena Campbell、Laijia Robinson、Calvin Miller、Joshua Christian、Louisa Amis、Nia Taylor、Cassandra Dill、Willie Davis、Stanley L. Evans、Eileen Brantley

  DOI：10.1016/j.bmcl.2014.05.089

  日期：2014.8

  A series of cinnamylideneacetophenones were synthesized via a modified Claisen-Schmidt condensation reaction and evaluated for cytotoxicity against breast cancer cells using the Alamar Blue (TM) assay. Derivatives 17 and 18 bearing a 2-nitro group on the B ring, exhibited sub-micromolar cytotoxicity in MCF-7 cells (IC50 = 71 and 1.9 nM), respectively. Derivative 17 also displayed sub-micromolar (IC50 = 780 nM) cytotoxicity in MDA-MB-468 cells. Additionally, 17 and 18 displayed significantly less cytotoxicity than the chemotherapeutic doxorubicin in non-tumorigenic MCF-10A cells. This study provides evidence supporting the continued development of nitro-substituted cinnamylideneacetophenones as small molecules to treat breast cancer. (C) 2014 Elsevier Ltd. All rights reserved.
• Further studies on anti-invasive chemotypes: An excursion from chalcones to curcuminoids
  作者：Bart I. Roman、Tine De Ryck、Sigrid Verhasselt、Marc E. Bracke、Christian V. Stevens

  DOI：10.1016/j.bmcl.2015.01.027

  日期：2015.3

  In our ongoing search for new anti-invasive chemotypes, we have made an excursion from previously reported potent 1,3-diarylpropenones (chalcones) to congeners bearing longer linkers between the aromatic moieties. Nine 1, x-diarylalkenones, including curcumin and bisdemethoxycurcumin, were evaluated in the chick heart invasion assay. Unfortunately, these compounds proved less potent and more toxic than earlier evaluated chemotypes. In the 1,3-diarylpenta-2,4-dien-1-one series, fluoro and/or trimethoxy substitution caused an increase in potency. This agrees with observations made earlier for the chalcone class. (C) 2015 Elsevier Ltd. All rights reserved.
• Structure-activity relationship studies and in vitro and in vivo anticancer activity of novel 3-aroyl-1,4-diarylpyrroles against solid tumors and hematological malignancies
  作者：Michela Puxeddu、Hongliang Shen、Ruoli Bai、Antonio Coluccia、Marianna Nalli、Carmela Mazzoccoli、Eleonora Da Pozzo、Chiara Cavallini、Claudia Martini、Viviana Orlando、Stefano Biagioni、Cristina Mazzoni、Addolorata Maria Luce Coluccia、Ernest Hamel、Te Liu、Romano Silvestri、Giuseppe La Regina

  DOI：10.1016/j.ejmech.2019.111828

  日期：2020.1

  Novel 3-aroyl-1,4-diarylpyrrole derivatives were synthesized to explore structure-activity relationships at the phenyls at positions 1 and 4 of the pyrrole. The presence of amino phenyl rings at positions 1 and 4 of the pyrrole ring were found to be a crucial requirement for potent antitumor activity. Several compounds strongly inhibited tubulin assembly through binding to the colchicine site. Compounds 42, 44, 48, 62 and 69 showed antitumor activity with low nanomolar 1050 values in several cancer cell lines. Compound 48 was generally more effective as an inhibitor of glioblastoma, colorectal and urinary bladder cancer cell lines; 69 consistently inhibited CML cell lines and demonstrated superiority in nilotinib and imatinib resistant LAMA84-R and KBM5-T3151 cells. In animal models, compound 48 exhibited significant inhibition of the growth of T24 bladder carcinoma and ES-2 ovarian clear cell carcinoma tumors. Compounds 48 and 69 represent robust lead compounds for the design of new broadspectrum anticancer agents active in different types of solid and hematological tumors. (C) 2019 Elsevier Masson SAS. All rights reserved.