3,5-bis-(3,4-dichlorophenylmethylene)piperidin-4-one

• 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: 3,5-bis-(3,4-dichlorophenylmethylene)piperidin-4-one
• 英文别名: 3,5-Bis[(3,4-dichlorophenyl)methylidene]piperidin-4-one
• 化学式: C₁₉H₁₃Cl₄NO
• 分子量: 413.13
• InChiKey: GJPXGFGIFQWUOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  草酰氯 、 3,5-bis-(3,4-dichlorophenylmethylene)piperidin-4-one 在 三乙胺 作用下， 以 1,2-二氯乙烷 为溶剂， 以64%的产率得到1,2-bis[3,5-bis(3,4-dichlorobenzylidene)-4-oxo-piperidin-1-yl]ethane-1,2-dione
  参考文献：
  名称：

  Novel 3,5-bis(arylidene)-4-piperidone dimers: Potent cytotoxins against colon cancer cells

  摘要：

  Two novel series of dimeric 3,5-bis(arylidene)-4-piperidones 7 and 8 were prepared as cytotoxic agents. A specific objective of this study was the discovery of novel compounds displaying potent anti-proliferative activities against colon cancers. Most of the compounds demonstrate potent cytotoxicity against HCT116 and HT29 colon cancer cell lines in which the IC50 values range from low micromolar to nanomolar values. In general, the majority of the compounds showed greater cytotoxicity and some degree of selectivity toward HCT116 cells compared to HT29 cells. Compound 9 in which the amidic carbonyl groups were excised was substantially less potent than 8a in both cell lines suggested that the amide groups are important components of the molecules for exhibiting cytotoxicity. Virtually all the compounds were more potent than a reference drug 5-fluorouracil which is used in treating colon cancers as well as a related enone curcumin. QSAR studies were undertaken and some guidelines for amplification of the project have been formulated. Flow cytometry analysis of a representative potent compound 7f revealed that it induces apoptosis in HCT116 cells. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.055
• 作为产物：
  描述：

  4-哌啶酮 、 3,4-二氯苯甲醛 在 sodium carbonate 作用下， 以51%的产率得到3,5-bis-(3,4-dichlorophenylmethylene)piperidin-4-one
  参考文献：
  名称：

  某些3,5-二芳基-4-哌啶酮和各种相关的季铵化合物及其类似物的细胞毒性评估

  摘要：

  在两个筛选中，主要制备了许多3,5-二亚芳基-4-哌啶酮（1）和一些相关的季铵盐（5）以及密切相关的类似物。第一个测试系统平均使用来自八种肿瘤疾病的54种人类肿瘤细胞系，即白血病，黑素瘤，结肠，非小细胞肺癌，小细胞肺癌，中枢神经系统，卵巢癌和肾癌。一些化合物证明了选择性毒性，特别是对白血病。第二个筛选使用L1210淋巴样白血病细胞。通常，在两次筛选中，该化合物的细胞毒性均低于参考药物美法仑。在Hammett（sigma），片段（f），1和5系列中的核取代基的摩尔折射率（MR）常数与人肿瘤细胞系和L1210细胞的IC50值。针对人类肿瘤细胞系的评估显示，f值的增加与系列1和5中细胞毒性的升高有关; MR常数在系列5中也很重要。在L1210筛查中，sigma和MR常数与细胞毒性呈正相关。X射线晶体学是对具有明显细胞毒性的3,5-双-[[[4'-（（甲硫基）苯基]亚甲基] -1-甲基-4-哌啶酮]甲硫脲（5d）和3

  DOI：

  10.1002/jps.2600830811

文献信息

• α,β-Unsaturated Carbonyl System of Chalcone-Based Derivatives Is Responsible for Broad Inhibition of Proteasomal Activity and Preferential Killing of Human Papilloma Virus (HPV) Positive Cervical Cancer Cells
  作者：Martina Bazzaro、Ravi K. Anchoori、Mohana Krishna R. Mudiam、Olga Issaenko、Srinivas Kumar、Balasubramanyam Karanam、Zhenhua Lin、Rachel Isaksson Vogel、Riccardo Gavioli、Federica Destro、Valeria Ferretti、Richard B. S. Roden、Saeed R. Khan

  DOI：10.1021/jm100589p

  日期：2011.1.27

  treatment of cervical cancer. We describe the synthesis and biological characterization of a new series of 1,3-diphenylpropen-1-one (chalcone) based derivatives lacking the boronic acid moieties of the previously reported chalcone-based proteasome inhibitor 3,5-bis(4-boronic acid benzylidene)-1-methylpiperidin-4-one and bearing a variety of amino acid substitutions on the amino group of the 4-piperidone.

  蛋白酶体抑制剂具有治疗宫颈癌的潜力。我们描述了一系列新的基于 1,3-diphenylpropen-1-one（查尔酮）的衍生物的合成和生物学表征，这些衍生物缺乏先前报道的基于查耳酮的蛋白酶体抑制剂 3,5-双（4-硼酸）的硼酸部分benzylidene)-1-methylpiperidin-4-one 并且在 4-piperidone 的氨基上带有多种氨基酸取代。我们的先导化合物2(RA-1) 抑制蛋白酶体活性，并在含有人乳头瘤病毒的宫颈癌细胞中具有改善的剂量依赖性抗增殖和促凋亡特性。此外，当与 FDA 批准的蛋白酶体抑制剂联合测试时，它会诱导协同杀死宫颈癌细胞系。我们的先导化合物使用计算机对接研究探索蛋白酶体抑制的潜在机制表明，其氧代哌啶部分的羰基容易受到蛋白酶体催化位点内 γ-羟基苏氨酸侧链的亲核攻击。
• WO2019/165229
  申请人：——

  公开号：——

  公开（公告）日：——
• Novel 3,5-bis(arylidene)-4-piperidone dimers: Potent cytotoxins against colon cancer cells
  作者：Swagatika Das、Umashankar Das、Deborah Michel、Dennis K.J. Gorecki、Jonathan R. Dimmock

  DOI：10.1016/j.ejmech.2013.03.055

  日期：2013.6

  Two novel series of dimeric 3,5-bis(arylidene)-4-piperidones 7 and 8 were prepared as cytotoxic agents. A specific objective of this study was the discovery of novel compounds displaying potent anti-proliferative activities against colon cancers. Most of the compounds demonstrate potent cytotoxicity against HCT116 and HT29 colon cancer cell lines in which the IC50 values range from low micromolar to nanomolar values. In general, the majority of the compounds showed greater cytotoxicity and some degree of selectivity toward HCT116 cells compared to HT29 cells. Compound 9 in which the amidic carbonyl groups were excised was substantially less potent than 8a in both cell lines suggested that the amide groups are important components of the molecules for exhibiting cytotoxicity. Virtually all the compounds were more potent than a reference drug 5-fluorouracil which is used in treating colon cancers as well as a related enone curcumin. QSAR studies were undertaken and some guidelines for amplification of the project have been formulated. Flow cytometry analysis of a representative potent compound 7f revealed that it induces apoptosis in HCT116 cells. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Cytotoxic Evaluation of Some 3,5-Diarylidene-4-piperidones and Various Related Quaternary Ammonium Compounds and Analogs
  作者：J.R. Dimmock、V.K. Arora、J.W. Quail、U. Pugazhenthi、T.M. Allen、G.Y. Kao、E. De Clercq

  DOI：10.1002/jps.2600830811

  日期：1994.8

  A number of 3,5-diarylidene-4-piperidones (1) and some related quaternary ammonium salts (5) as well as closely related analogs were prepared principally as candidate cytotoxic agents in two screens. The first test system used an average of 54 human tumor cell lines from eight neoplastic diseases, namely leukemia, melanoma, colon, non-small-cell lung, small-cell lung, central nervous system, ovarian

  在两个筛选中，主要制备了许多3,5-二亚芳基-4-哌啶酮（1）和一些相关的季铵盐（5）以及密切相关的类似物。第一个测试系统平均使用来自八种肿瘤疾病的54种人类肿瘤细胞系，即白血病，黑素瘤，结肠，非小细胞肺癌，小细胞肺癌，中枢神经系统，卵巢癌和肾癌。一些化合物证明了选择性毒性，特别是对白血病。第二个筛选使用L1210淋巴样白血病细胞。通常，在两次筛选中，该化合物的细胞毒性均低于参考药物美法仑。在Hammett（sigma），片段（f），1和5系列中的核取代基的摩尔折射率（MR）常数与人肿瘤细胞系和L1210细胞的IC50值。针对人类肿瘤细胞系的评估显示，f值的增加与系列1和5中细胞毒性的升高有关; MR常数在系列5中也很重要。在L1210筛查中，sigma和MR常数与细胞毒性呈正相关。X射线晶体学是对具有明显细胞毒性的3,5-双-[[[4'-（（甲硫基）苯基]亚甲基] -1-甲基-4-哌啶酮]甲硫脲（5d）和3