4-[3,5-bis(2-fluorobenzylidene)-4-oxo-piperidin-1-yl]-4-oxo-butanoic acid | 600637-08-9

• 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: 4-[3,5-bis(2-fluorobenzylidene)-4-oxo-piperidin-1-yl]-4-oxo-butanoic acid
• 英文别名: 4-[3,5-Bis[(2-fluorophenyl)methylidene]-4-oxopiperidin-1-yl]-4-oxobutanoic acid；4-[3,5-bis[(2-fluorophenyl)methylidene]-4-oxopiperidin-1-yl]-4-oxobutanoic acid
• CAS: 600637-08-9
• 化学式: C₂₃H₁₉F₂NO₄
• 分子量: 411.405
• InChiKey: JOCVIXCOAVYABF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  74.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-羟基丁二酰亚胺 、 4-[3,5-bis(2-fluorobenzylidene)-4-oxo-piperidin-1-yl]-4-oxo-butanoic acid 在 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以81%的产率得到
  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：

  丁二酸酐 、 EF24 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以92%的产率得到4-[3,5-bis(2-fluorobenzylidene)-4-oxo-piperidin-1-yl]-4-oxo-butanoic acid
  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

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.