(3E,5E)-3,5-dibenzylidenepiperidin-4-one 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: (3E,5E)-3,5-dibenzylidenepiperidin-4-one hydrochloride
• 英文别名: (3E,5E)-3,5-dibenzylidenepiperidin-4-one;hydrochloride
• 化学式: C₁₉H₁₇NO*ClH
• 分子量: 311.811
• InChiKey: TUYFFZOIQLBJAY-OYJDLGDISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.75
• 重原子数：
  22
• 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：

  (3E,5E)-3,5-dibenzylidenepiperidin-4-one hydrochloride 在 1-丙基磷酸酐 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 N-{3-[4-(3-aminopropylamino)butylamino]propyl}-4-[3,5-dibenzylidene-4-oxopiperidin-1-yl]-4-oxobutanamide tri(trifluoroacetate)
  参考文献：
  名称：

  多胺共轭作为在阿尔茨海默氏病框架内靶向淀粉样蛋白聚集的有前途的策略

  摘要：

  精胺缀合物2 - 6，携带各种装饰3,5- dibenzylidenepiperidin -4-酮作为生物活性动机，被设计成引导antiaggregating属性到线粒体，使用多胺的功能的车辆的工具。研究证实线粒体邻苯二酚衍生物2的进口对Aβ诱导的毒性具有有效的抗聚集活性和神经保护作用。值得注意的是，还没有阐明聚胺基序在Aβ分子识别中的关键功能。在计算机模拟研究的支持下，该实验读数为聚胺的作用提供了重要的新见解。因此，我们提出多胺缀合作为开发神经保护剂导线的有前途的策略，可能有助于破译Aβ毒性的复杂图景。

  DOI：

  10.1021/acsmedchemlett.6b00339
• 作为产物：
  描述：

  4-氧代哌啶酮盐酸盐 、 苯甲醛 在 盐酸 、 溶剂黄146 作用下， 反应 48.0h， 以57%的产率得到(3E,5E)-3,5-dibenzylidenepiperidin-4-one hydrochloride
  参考文献：
  名称：

  多胺共轭作为在阿尔茨海默氏病框架内靶向淀粉样蛋白聚集的有前途的策略

  摘要：

  精胺缀合物2 - 6，携带各种装饰3,5- dibenzylidenepiperidin -4-酮作为生物活性动机，被设计成引导antiaggregating属性到线粒体，使用多胺的功能的车辆的工具。研究证实线粒体邻苯二酚衍生物2的进口对Aβ诱导的毒性具有有效的抗聚集活性和神经保护作用。值得注意的是，还没有阐明聚胺基序在Aβ分子识别中的关键功能。在计算机模拟研究的支持下，该实验读数为聚胺的作用提供了重要的新见解。因此，我们提出多胺缀合作为开发神经保护剂导线的有前途的策略，可能有助于破译Aβ毒性的复杂图景。

  DOI：

  10.1021/acsmedchemlett.6b00339

文献信息

• Cytotoxic N-[4-(3-aryl-3-oxo-1-propenyl)phenylcarbonyl]-3,5-bis(phenylmethylene)-4-piperidones and related compounds
  作者：J Dimmock

  DOI：10.1016/s0223-5234(02)01414-9

  日期：2002.12.1

  5-bis(phenylmethylene)-4-piperidone (2) giving rise to a novel series of N-[4-(3-aryl-3-oxo-1-propenyl)phenylcarbonyl]-3,5-bis(phenylmethylene)-4-piperidones (3). Molecular simplification of the amides 3 led to the formation of the corresponding N-(3-aryl-1-oxo-2-propenyl)-3,5-bis(phenylmethylene)-4-piperidones (4). A cytotoxic evaluation of the compounds in series 1-4 utilized murine P388 and L1210 cells as well

  制备了一系列的4-羧基查耳酮1并将其与3,5-双（苯基亚甲基）-4-哌啶酮（2）偶联，产生了一系列新的N- [4-（3-芳基-3-氧代-1-） （丙烯基）苯基羰基] -3，5-双（苯基亚甲基）-4-哌啶酮（3）。酰胺3的分子简化导致形成相应的N-（3-芳基-1-氧代-2-丙烯基）-3，5-双（苯基亚甲基）-4-哌啶酮（4）。1-4系列化合物的细胞毒性评估利用了鼠P388和L1210细胞以及人Molt 4 / C8和CEM T淋巴细胞。通常，这些化合物显示出明显的毒性。当考虑所有四个筛选时，54％烯酮的IC（50）值小于10 microM，而在P388分析中，系列3的所有成员的IC（50）值小于1 microM。在系列1的化合物的效力之间建立了各种相关性 3和4以及Hammett sigma，Hansch pi和芳基取代基的分子折射率常数。通过X射线晶体学测定了系列3和4中五个代表性化合物的
• Design, synthesis, and antihypertensive activity of curcumin-inspired compounds via ACE inhibition and vasodilation, along with a bioavailability study for possible benefit in cardiovascular diseases
  作者：Li-chun Wang、Xiao-dong Zhuang、Li-zhen Liao、Xiao-bian Dong、Xun Hu、Yue Guo、Zhi-min Du、Xin-xue Liao

  DOI：10.2147/dddt.s96315

  日期：——

  This study describes the synthesis of a novel series of curcumin-inspired compounds via a facile synthetic route. The structures of these derivatives were ascertained using various spectroscopic and analytic techniques. The pharmacological effects of the target analogs were assessed by assaying their inhibition of angiotensin-converting enzyme (ACE). All of the synthesized derivatives exhibited considerable

  这项研究描述了通过简便的合成途径合成一系列新的姜黄素类化合物。使用各种光谱学和分析技术确定这些衍生物的结构。通过测定靶类似物对血管紧张素转化酶（ACE）的抑制作用来评估其药理作用。所有合成的衍生物均显示出对ACE的显着抑制，其最大抑制浓度的一半为1.23至120.32μM。在与睾丸ACE（tACE）的对接分析中，最有前途的抑制剂（4j）被有效地容纳在蛋白腔的深裂中，与Glu162，His353和Ala356的原子间紧密接触，与赖诺普利相当。化合物4i，4j，4k，使用Langendorff技术，进一步选择4l和4l来确定其在离体大鼠心脏上的血管舒张活性（心输出量和中风量）。在实验小鼠中测定化合物4j的生物利用度。
• Synthesis and structural determination of 3,5-bis(2-fluorobenzylidene)-4-piperidone analogs of curcumin
  作者：Pallavi Lagisetty、Douglas R. Powell、Vibhudutta Awasthi

  DOI：10.1016/j.molstruc.2009.07.016

  日期：2009.11

  Analogs of cytotoxic compound 3,5-bis(2-fluorobenzylidene)-4-piperidone (1) were synthesized and their molecular structures were characterized by H-1, C-13 NMR, ESI-MS, IR spectra and X-ray crystallography. The central ring of the piperidin-4-one ring assumes a sofa conformation with two benzylidene rings connected through E, E oriented groups. The compound 1 crystallized in triclinic space group P (1) over bar. In order to obtain potentially more efficacious compounds, three dimers of 3,5-bis(2-fluorobenzylidene)-4-piperidone were synthesized. The two molecules of 1 were conjugated together via -N-oxalyl-N- (3), -N-fumaryl-N- (4) or -N-DTPA-N- (5) linkers. Compound 3 crystallized in monoclinic space group P2(1)/n. (C) 2009 Elsevier B. V. All rights reserved.
• Syntheses of 4-(3,5-Bisphenylmethylene-4-oxo-piperidin-1-yl)-4-oxo-but-2<b><i>Z</i></b>-enoic Acid Arylamides as Candidate Cytotoxic Agents
  作者：Amitabh Jha、Jonathan R. Dimmock

  DOI：10.1081/scc-120017198

  日期：2003.1.5

  The title compounds were designed and synthesized as candidate cytotoxic agents. They were synthesized by reacting 3,5-bisphenylmethylene-piperidin-4-one with the appropriate 3-arylcarbamoylacrylic acids. These reactions follow an unusual mechanism and deviate from the previously reported reactions on similar substrates.
• Curcumin-inspired cytotoxic 3,5-bis(arylmethylene)-1-(N-(ortho-substituted aryl)maleamoyl)-4-piperidones: A novel group of topoisomerase II alpha inhibitors
  作者：Amitabh Jha、Katherine M. Duffield、Matthew R. Ness、Sujatha Ravoori、Gabrielle Andrews、Khushwant S. Bhullar、H.P. Vasantha Rupasinghe、Jan Balzarini

  DOI：10.1016/j.bmc.2015.08.023

  日期：2015.10

  Three series of novel 3,5-bis(arylmethylene)-1-(N-(ortho-substituted aryl)maleamoyl)-4-piperidones, designed as simplified analogs of curcumin with maleic diamide tether, were synthesized and bioevaluated. These compounds displayed potent cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 leukemic cells. In contrast, the related N-arylmaleamic acids possessed little or no cytotoxicity in these three screens. Design of these compounds was based on molecular modeling studies performed on a related series of molecule in a previous study. Representative title compounds were found to be significantly potent in inhibiting the activity of topoisomerase II alpha indicating the possible mode of action of these compounds. These compounds were also potent antioxidants in vitro and attenuated the AAPH triggered peroxyl radical production in human fibroblasts. Various members of these series were also well tolerated in both in vitro and in vivo toxicity analysis. (C) 2015 Elsevier Ltd. All rights reserved.