3,5-bis(4-chlorobenzylidene)-4-piperidone hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 3,5-bis(4-chlorobenzylidene)-4-piperidone hydrochloride
• 英文别名: 3,5-Bis[(4-chlorophenyl)methylidene]piperidin-4-one;hydrochloride
• 化学式: C₁₉H₁₅Cl₂NO*ClH
• 分子量: 380.701
• InChiKey: ATKSBCRDKVUKSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.05
• 重原子数：
  24
• 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：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,5-bis(4-chlorobenzylidene)-4-piperidone hydrochloride 在 potassium carbonate 作用下， 以1.5 g的产率得到3,5-bis(4-chlorobenzylidene)piperidin-4-one
  参考文献：
  名称：

  CLEFMA—An anti-proliferative curcuminoid from structure–activity relationship studies on 3,5-bis(benzylidene)-4-piperidones

  摘要：

  3,5-Bis(benzylidene)-4-piperidones are being advanced as synthetic analogs of curcumin for anti-cancer and anti-inflammatory properties. We performed structure-activity relationship studies, by testing several synthesized 3,5-bis(benzylidene)-4-piperidones for anti-proliferative activity in lung adenocarcinoma H441 cells. Compared to the lead compound 1, or 3,5-bis(2-fluorobenzylidene)-4-piperidone, five compounds were found to be more potent (IC50 <30 mu M), and 16 compounds possessed reduced cell-killing efficacy (IC50 >50 mu M). Based on the observations, we synthesized 4-[3,5-bis(2-chlorobenzyl-idene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid] (29 or CLEFMA) as a novel analog of 1. CLEFMA was evaluated for anti-proliferative activity in H441 cells, and was found to be several folds more potent than compound 1. We did not find apoptotic cell population in flow cytometry, and the absence of apoptosis was confirmed by the lack of caspase cleavage. The electron microscopy of H441cells indicated that CLEFMA and compound 1 induce autophagic cell death that was inhibited by specific autophagy inhibitor 3-methyladenine. The results suggest that the potent and novel curcuminoid, CLEFMA, offers an alternative mode of cell death in apoptosis-resistant cancers. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.055
• 作为产物：
  描述：

  4-哌啶酮 、 4-氯苯甲醛 以51%的产率得到3,5-bis(4-chlorobenzylidene)-4-piperidone hydrochloride
  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

• CLEFMA—An anti-proliferative curcuminoid from structure–activity relationship studies on 3,5-bis(benzylidene)-4-piperidones
  作者：Pallavi Lagisetty、Prachi Vilekar、Kaustuv Sahoo、Shrikant Anant、Vibhudutta Awasthi

  DOI：10.1016/j.bmc.2010.06.055

  日期：2010.8

  3,5-Bis(benzylidene)-4-piperidones are being advanced as synthetic analogs of curcumin for anti-cancer and anti-inflammatory properties. We performed structure-activity relationship studies, by testing several synthesized 3,5-bis(benzylidene)-4-piperidones for anti-proliferative activity in lung adenocarcinoma H441 cells. Compared to the lead compound 1, or 3,5-bis(2-fluorobenzylidene)-4-piperidone, five compounds were found to be more potent (IC50 <30 mu M), and 16 compounds possessed reduced cell-killing efficacy (IC50 >50 mu M). Based on the observations, we synthesized 4-[3,5-bis(2-chlorobenzyl-idene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid] (29 or CLEFMA) as a novel analog of 1. CLEFMA was evaluated for anti-proliferative activity in H441 cells, and was found to be several folds more potent than compound 1. We did not find apoptotic cell population in flow cytometry, and the absence of apoptosis was confirmed by the lack of caspase cleavage. The electron microscopy of H441cells indicated that CLEFMA and compound 1 induce autophagic cell death that was inhibited by specific autophagy inhibitor 3-methyladenine. The results suggest that the potent and novel curcuminoid, CLEFMA, offers an alternative mode of cell death in apoptosis-resistant cancers. (C) 2010 Elsevier Ltd. 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