(E)-3-(2-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one | 151703-82-1

• 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)-3-(2-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 151703-82-1
• 化学式: C₁₉H₂₀O₅
• 分子量: 328.365
• InChiKey: ZGKZOUPOGPHCRJ-MDZDMXLPSA-N

物化性质

• 熔点：
  127-129 °C
• 沸点：
  496.4±45.0 °C(predicted)
• 密度：
  1.148±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 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：

  (E)-3-(2-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one 在 对甲基苯磺酰甲基异腈 、 copper diacetate 、 sodium hydride 、 三乙胺 作用下， 以 乙醚 、 二甲基亚砜 、 1,2-二氯乙烷 、 mineral oil 为溶剂， 反应 22.0h， 生成 3-(2-methoxyphenyl)-1-phenyl-4-(3,4,5-trimethoxyphenyl)-1H-pyrrole
  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：

  3',4',5'-三甲氧基苯乙酮 、 邻甲氧基苯甲醛 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 (E)-3-(2-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  作为具有抗肿瘤效力的微管蛋白聚合抑制剂的一系列新型苯并噻嗪衍生物

  摘要：

  在这项工作中，合成并筛选了一系列二芳基苯并[ b ] [1,4] 硫氮杂衍生物D1-D36作为具有抗肿瘤效力的微管蛋白聚合抑制剂。它们是通过首次引入七元环苯并噻嗪作为 CA-4 修饰的接头而设计的。其中，命中化合物D8显示出抑制多种癌细胞系生长的潜力（IC 50值：HeLa 1.48 μM，MCF-7 1.47 μM，HT29 1.52 μM 和 A549 1.94 μM），与阳性对照秋水仙碱和CA-4P。D8的计算 IC 50值作为微管蛋白聚合抑制剂的浓度为 1.20 μM。流式细胞术检测结果表明，D8可以诱导有丝分裂灾难和活癌细胞的死亡。D8还表明了抗血管活性。对接模拟暗示了可能的结合模式，推断引入与附近微管蛋白链相互作用的可能性。由于新的结构试验已经进行了初步讨论，这项工作可能会激发进一步修改微管蛋白相关抗癌药物和治疗方法的新思路。

  DOI：

  10.1016/j.bioorg.2020.104585

文献信息

• Design, synthesis, and biological evaluation of thiophene analogues of chalcones
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Maria Dora Carrion、Carlota Lopez Cara、Olga Cruz-Lopez、Delia Preti、Manlio Tolomeo、Stefania Grimaudo、Antonella Di Cristina、Nicola Zonta、Jan Balzarini、Andrea Brancale、Taradas Sarkar、Ernest Hamel

  DOI：10.1016/j.bmc.2008.04.026

  日期：2008.5

  Chalcones are characterized by possessing an enone moiety between two aromatic rings. A series of chalcone-like agents, in which the double bond of the enone system is embedded within a thiophene ring, were synthesized and evaluated for antiproliferative activity and inhibition of tubulin assembly and colchicine binding to tubulin. The replacement of the double bond with a thiophene maintains antiproliferative activity and therefore must not significantly alter the relative conformation of the two aryl rings. The synthesized compounds were found to inhibit the growth of several cancer cell lines at nanomolar to low micromolar concentrations. In general, all compounds having significant antiproliferative activity inhibited tubulin polymerization with an IC50 < 2 mu M. Several of these compounds caused K562 cells to arrest in the G2/M phase of the cell cycle. (C) 2008 Elsevier Ltd. All rights reserved.
• Holt Jr., Herman; LeBlanc, Regan; Dickson, John, Heterocyclic Communications, 2005, vol. 11, # 6, p. 465 - 470
  作者：Holt Jr., Herman、LeBlanc, Regan、Dickson, John、Brown, Toni、Maddox, Jessica R.、Lee, Moses

  DOI：——

  日期：——
• Synthesis and cytotoxicity of epoxide and pyrazole analogs of the combretastatins
  作者：Regan LeBlanc、John Dickson、Toni Brown、Michelle Stewart、Hari N. Pati、Don VanDerveer、Hadi Arman、Jeff Harris、William Pennington、Herman L. Holt、Moses Lee

  DOI：10.1016/j.bmc.2005.06.028

  日期：2005.11

  Twenty-six epoxide and corresponding pyrazole derivatives, of the structurally related chalcones and combretastatin A-4 (CA-4), were synthesized and tested for in vitro cytotoxicity. These molecules were synthesized by epoxidation of the relevant chalcones, followed by reaction with hydrazine. The structures of epoxides 3 and 7, and pyrazole 17, were confirmed by X-ray diffraction studies. The relatively coplanar conformation of a 3',3",4',4",5',5"-hexamethoxypyrazole 17 was in good agreement with the shape for 3',3",4',4",5'-pentamethoxypyrazole 16, which was determined from molecular mechanics optimization. In vitro cytotoxicity of each class of compounds was obtained using a 72 h continuous exposure MTT assay against two murine cancer cell lines; B16 melanoma and L1210 leukemia. The effect of substitution in the A-ring is addressed: three methoxy groups versus two, generally increased cytotoxicity across both cell lines. In the majority of cases, the pyrazoles are generally more active than the epoxides, with the most active, 5-(3"-amino-4"-methoxyphenyl)-3-(3',4',5'-trimethoxyphenyl)pyrazole 21, possessing an IC50 value of 5 and 2.4 mu M (B16 and L1210, respectively). Due to their planar conformations, the pyrazoles are typically less active than the corresponding chalcones, which adopt angular conformations similar to CA-4. B-ring modifications confirmed that in general the amino compounds are more active than the corresponding nitro compounds. Varying the number and orientation of methoxy groups on the A-ring did not produce any significant differences in toxicity in the cell lines studied. (c) 2005 Elsevier Ltd. All rights reserved.
• Design, synthesis, and biological testing of pyrazoline derivatives of combretastatin-A4
  作者：Marlie Johnson、Brent Younglove、Lauren Lee、Regan LeBlanc、Herman Holt、Patrice Hills、Hilary Mackay、Toni Brown、Susan L. Mooberry、Moses Lee

  DOI：10.1016/j.bmcl.2007.07.105

  日期：2007.11

  Fourteen N-acetylated and non-acetylated 3,4,5-tri- or 2,5-dimethoxypyrazoline analogs of combretastatin-A4 (1) were synthesized. A non-acetylated derivative (5a) with the same substituents as CA-4 (1) was the most active compound in the series, with IC50 values of 2.1 and 0.5 mu M in B16 and L1210 cell lines, respectively. In contrast, a similar compound with an acetyl group at N1 of the pyrazoline ring (6g) showed poor activity in the cell lines studied. A cell-based assay indicated that compound 5a caused extensive microtubule depolymerization with an EC50 value of 7.1 mu M in A-10 cells while no activity was seen with the acetylated compound. Molecular modeling studies showed that these compounds possess a twisted conformation similar to CA-4 (1). (c) 2007 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.