3,5-bis(benzylidene)-4-piperidone

• 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(benzylidene)-4-piperidone
• 英文别名: 3,5-Dibenzylidenepiperidin-4-one
• 化学式: C₁₉H₁₇NO
• 分子量: 275.35
• InChiKey: KPVTZSGWKGUMLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 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：

  3,5-bis(benzylidene)-4-piperidone 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 0.5h， 生成 4,5-(diphenyl)pyrrolo(spiro[2.3']oxindole)spiro[3.3"]-5"-(phenylmethylidene)-1"-N-acrolylpiperidin-4"-one
  参考文献：
  名称：

  Synthesis and discovery of highly functionalized mono- and bis-spiro-pyrrolidines as potent cholinesterase enzyme inhibitors

  摘要：

  Novel mono and bis spiropyrrolidine derivatives were synthesized via an efficient ionic liquid mediated, 1,3-dipolar cycloaddition methodology and evaluated in vitro for their AChE and BChE inhibitory activities in search for potent cholinesterase enzyme inhibitors. Most of the synthesized compounds displayed remarkable AChE inhibitory activities with IC50 values ranging from 1.68 to 21.85 mu M, wherein compounds 8d and 8j were found to be most active inhibitors against AChE and BChE with IC50 values of 1.68 and 2.75 mu M, respectively. Molecular modeling simulation on Torpedo californica AChE and human BChE receptors, showed good correlation between IC50 values and binding interaction template of the most active inhibitors docked into the active site of their relevant enzymes. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.019
• 作为产物：
  描述：

  3,5-dibenzylidene-4-piperidone hydrochloride 在 potassium carbonate 作用下， 以2.1 g的产率得到3,5-bis(benzylidene)-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

• Synthesis and antimicrobial activity of new 3,5-diarylidene-4-piperidone derivatives
  作者：Kulathooran Singaram、Dhamodaran Marimuthu、Selvakumar Baskaran、Venkataraman Ramaswamy

  DOI：10.2298/jsc151112043s

  日期：——

  Three series of heteroaromatic analogs (twenty seven compounds) with monoketone linkers have been synthesized and evaluated for their antimicrobial activity against six microbial strains. Among them, 3,5-dibenzylidene-1-(3,5-dichloro-2-hydroxyphenylsulfonyl)piperidin-4-one 5e showed best antifungal activity against Aspergillus niger and Aspergillus fumigatus. Structural elucidation of the synthesized compounds was determined on the basis of various spectroscopic methods.

  我们合成了三个系列的杂芳香族类似物（二十七个化合物），它们都带有 合成并评估了它们对六种微生物菌株的抗菌活性。 对六种微生物菌株的抗菌活性进行了评估。其中包括 3,5-二苄基-1-(3,5-二氯-2-羟基苯磺酰基)哌啶-4-酮 5e 对黑曲霉和烟曲霉显示出最佳的抗真菌活性。 和烟曲霉的抗真菌活性最好。合成化合物的结构阐释是根据各种光谱测定的 根据各种光谱方法确定了合成化合物的结构。
• 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
• Synthesis, human topoisomerase IIα inhibitory properties and molecular modeling studies of anti-proliferative curcumin mimics
  作者：Nehmedo G. Fawzy、Siva S. Panda、Walid Fayad、ElSayed M. Shalaby、Aladdin M. Srour、Adel S. Girgis

  DOI：10.1039/c9ra05661k

  日期：——

  Piperidinecarboxamides (curcumin mimics) show promising anti-proliferative properties against HCT116 (colon), MCF7 (breast) and A431 (squamous skin) carcinoma cell lines with potency higher than that of 5-fluorouracil.

  吡啶甲酰胺（姜黄素类似物）显示出对HCT116（结肠）、MCF7（乳腺）和A431（鳞状皮肤）癌细胞系有很好的抗增殖特性，其效力高于5-氟尿嘧啶。
• Dimeric 3,5-bis(benzylidene)-4-piperidones: A novel cluster of tumour-selective cytotoxins possessing multidrug-resistant properties
  作者：Swagatika Das、Umashankar Das、Hiroshi Sakagami、Naoki Umemura、Shoko Iwamoto、Tomohiko Matsuta、Masami Kawase、Joseph Molnár、Julianna Serly、Dennis K.J. Gorecki、Jonathan R. Dimmock

  DOI：10.1016/j.ejmech.2012.02.042

  日期：2012.5

  A series of bis[3,5-bis(benzylidene)-4-oxo-1-piperidinyl]amides 1 display potent cytotoxic properties towards a wide range of tumours. A number of the CC50 and IC50 values are in the range of 10−8 M. Specifically, these compounds have the following important properties. First, greater toxicity was demonstrated towards certain tumours than various non-malignant cells. Second, various compounds in series

  一系列双[3,5-双（亚苄基）-4-氧代-1-哌啶基]酰胺1对多种肿瘤均表现出强力的细胞毒性。CC 50和IC 50的值在10 -8  M的范围内。具体地，这些化合物具有以下重要的性质。首先，证明了对某些肿瘤的毒性要大于各种非恶性细胞。第二，系列1中的各种化合物对许多人类结肠癌和白血病细胞有毒性。第三，这些化合物逆转了P-gp介导的多药耐药性。各种原型分子，例如1a，b和1i被鉴定为铅分子有待进一步研究。代表性的铅分子1b通过核内体DNA片段化和PARP裂解在HSC-2和HL-60细胞中诱导凋亡，而流式细胞仪显示该化合物在人结肠癌HCT-116的细胞周期中阻断了G2 / M和S期细胞。
• Dispiropyrrolidinyl-piperidone embedded indeno[1,2-b]quinoxaline heterocyclic hybrids: Synthesis, cholinesterase inhibitory activity and their molecular docking simulation
  作者：Natarajan Arumugam、Abdulrahman I. Almansour、Raju Suresh Kumar、D. Kotresha、R. Saiswaroop、S. Venketesh

  DOI：10.1016/j.bmc.2019.03.058

  日期：2019.6

  indono[1,2-b]quinoxaline heterocyclic hybrids 7a-j were synthesized employing multicomponent 1,3-dipolar cycloaddition strategy in [bmim]Br. The azomethine ylide employed is first of its kind and generated in situ from indenoquinoxalinone and l-tryptophan, a combination that has not been employed previously for the in situ generation of azomethine ylides. The synthesized heterocyclic hybrids 7a-j were evaluated

  使用[bmim] Br中的多组分1,3-偶极环加成策略合成了一个小型的新型双螺并吡咯烷基-哌啶酮系链的吲哚[1,2-b]喹喔啉杂环杂种7a-j。所使用的偶氮甲碱叶立德是这种类型的，并且是由茚并喹喔啉酮和1-色氨酸原位产生的，这是先前尚未用于原位产生偶氮甲碱的组合。评价了合成的杂环杂种7a-j的体外乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）抑制活性，其中化合物7h和7j比标准药物对AChE和BChE的酶抑制作用更强，IC50值为3.22、2.01，分别为12.40和10.45 mM。