(E)-3-(2-chlorophenyl)-1-(3,4,5-trimethoxyphenyl)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)-3-(2-chlorophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• 化学式: C₁₈H₁₇ClO₄
• 分子量: 332.784
• InChiKey: OFHSHAYWPLGPQG-CMDGGOBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 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：

  (E)-3-(2-chlorophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-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98%的产率得到(4-(2-chlorophenyl)-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：

  3',4',5'-三甲氧基苯乙酮 、 2-氯苯甲醛 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 (E)-3-(2-chlorophenyl)-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

• 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.
• A novel series of benzothiazepine derivatives as tubulin polymerization inhibitors with anti-tumor potency
  作者：Bin Wang、Li-Ren Wang、Lu-Lu Liu、Wei Wang、Ruo-Jun Man、Da-Jun Zheng、Yu-Shan Deng、Yu-Shun Yang、Chen Xu、Hai-Liang Zhu

  DOI：10.1016/j.bioorg.2020.104585

  日期：2021.3

  In this work, a series of diaryl benzo[b][1,4]thiazepine derivatives D1-D36 were synthesized and screened as tubulin polymerization inhibitors with anti-tumor potency. They were designed by introducing the seven-member ring benzothiazepine as the linker for CA-4 modification for the first time. Among them, the hit compound D8 showed potential on inhibiting the growth of several cancer cell lines (IC50

  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。