3,5-bis(4-dimethylaminobenzylidene)-4-piperidone | 92520-33-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3,5-bis(4-dimethylaminobenzylidene)-4-piperidone
• 英文别名: 3,5-bis[4-(dimethylamino)benzylidene]-4-oxopiperidine；3,5-Bis[[4-(dimethylamino)phenyl]methylidene]piperidin-4-one
• CAS: 92520-33-7
• 化学式: C₂₃H₂₇N₃O
• 分子量: 361.487
• InChiKey: PQXIGFCAMSKVHL-UHFFFAOYSA-N

物化性质

• 沸点：
  587.8±50.0 °C(Predicted)
• 密度：
  1.164±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  草酰氯 、 3,5-bis(4-dimethylaminobenzylidene)-4-piperidone 在 三乙胺 作用下， 以 1,2-二氯乙烷 为溶剂， 以46%的产率得到1,2-bis[3,5-bis{4-(N,N-dimethylamino)benzylidene}-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：

  3,5-bis(4-(dimethylamino)benzylidene)-4-piperidone hydrochloride 在 potassium carbonate 作用下， 以0.6 g的产率得到3,5-bis(4-dimethylaminobenzylidene)-4-piperidone
  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

• Novel Conjugated Unsaturated Ketones with Submicromolar Potencies Towards some Leukemic and Colon Cancer Cells
  作者：Swagatika Das、H. Inci Gul、Umashankar Das、Jan Balzarini、Stephen G. Dimmock、Jonathan R. Dimmock

  DOI：10.2174/1573406414666181015142633

  日期：2019.5.20

  compounds to treat this devastating condition. Various alkylating anticancer drugs have been employed in the clinic for treating cancers. Unsaturated conjugated ketones are a group of alkylators which are of significant interest as potent antineoplastic agents. Objective: The goal of this study is to discover unsaturated conjugated ketones which are novel potent cytotoxins displaying growth-inhibitory

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  申请人：合肥工业大学

  公开号：CN107721914B

  公开（公告）日：2021-02-26

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• Structure activity relationship analysis of antiproliferative cyclic C5-curcuminoids without DNA binding: Design, synthesis, lipophilicity and biological activity
  作者：Imre Huber、Zsuzsanna Rozmer、Zoltán Gyöngyi、Ferenc Budán、Péter Horváth、Eszter Kiss、Pál Perjési

  DOI：10.1016/j.molstruc.2019.127661

  日期：2020.4

  shortcomings. The synthesis of twenty cyclic C5-curcuminoids is described in this study in order to gain more insight into their anticancer structure-activity relationship (SAR). The design of their synthesis included four different cyclanones and five substituted aromatic aldehydes to form four, five-membered subgroups. These model compounds were evaluated in vitro for antiproliferative activity in an XTT

  摘要 姜黄素结构中两个芳环之间的 β-二酮接头对水解和代谢的化学敏感性使得研究没有这些缺点的姜黄素结构修饰类似物变得至关重要。本研究描述了 20 种环状 C5-姜黄素的合成，以便更深入地了解它们的抗癌结构-活性关系 (SAR)。他们的合成设计包括四种不同的环酮和五种取代的芳香醛，以形成四个五元亚组。在针对 MCF-7 人非侵入性乳腺癌细胞和 Jurkat 人 T 淋巴细胞白血病细胞的 XTT 细胞活力测定中，在体外评估了这些模型化合物在五种不同浓度（10 nM、100 nM、1 μM、10 μM 和 20 μM）。大多数研究的化合物显示出显着的细胞毒性，IC50 值在 120 nM 和 2 μM 范围内，对姜黄素的相对毒性值非常高。得出并总结了 SAR 结论。开发了一种方法并应用于基于 TLC 的实验 logP 测量，这是此类 C5-姜黄素的新方法。logP 数据和结构修改显示出很强的相关性。根据
• Phosphoryl Substituted 3,5-<i>Bis</i>(Arylidene)-4-Piperidones Posessing High Antitumor Activity
  作者：I. L. Odinets、M. V. Makarov、O. I. Artyushin、E. Yu. Rybalkina、K. A. Lyssenko、T. V. Timofeeva、M. Yu. Antipin

  DOI：10.1080/10426500701793246

  日期：2008.1.14

  3,5-Bis(arylidene)-4-piperidones and related compounds 1 possess anticancer and antioxidant activity (Scheme 1).1,2 Some of these compounds are also fluorescent, which makes possible to use them as dyes for tracing their cellular pathways during chemotherapy and as agents for photodynamic therapy.3 The important way to regulate the bioavailability and drug delivery of these compounds to target organs

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• Novel Biologically Active 1,3,2-Oxazaphosphinane Derivatives
  作者：Anatolii E. Shipov、Galina K. Genkina、Pavel V. Petrovskii、Evgenii I. Goryunov、Michael V. Makarov

  DOI：10.1080/10426507.2010.520281

  日期：2011.3.31