3,5-bis(2-chlorobenzylidene)-4-piperidone | 342808-26-8

• 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(2-chlorobenzylidene)-4-piperidone
• 英文别名: 3,5-Bis (2-chlorobenzylidene)piperidin-4-one；3,5-bis[(2-chlorophenyl)methylidene]piperidin-4-one
• CAS: 342808-26-8
• 化学式: C₁₉H₁₅Cl₂NO
• 分子量: 344.24
• InChiKey: RVBVBUPGVORCBH-UHFFFAOYSA-N

物化性质

• 沸点：
  553.5±50.0 °C(Predicted)
• 密度：
  1.331±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 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(2-chlorobenzylidene)-4-piperidone 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 2.0h， 生成 spiro-[2.3']-oxindolespiro[3.3"]-1"-carbonyl(spiro[2.3']oxindole-5-phenylpyrrolo)-5"-(2-chlorophenylmethylidene)tetrahydro-4"-(1H)-pyridinone-4-(2-chlorophenyl)-5-phenylpyrrolidine
  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-bis (2-chlorobenzylidene)-4-piperidone hydrochloride 在 potassium carbonate 作用下， 以1.3 g的产率得到3,5-bis(2-chlorobenzylidene)-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

• 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。
• Design, synthesis, and biological evaluation of novel &lt;strong&gt;EF24 &lt;/strong&gt;and &lt;strong&gt;EF31 &lt;/strong&gt;analogs as potential I&amp;kappa;B kinase &amp;beta; inhibitors for the treatment of pancreatic cancer
  作者：Xuemeng Xie、Jinfu Tu、Heyi You、Bingren Hu

  DOI：10.2147/dddt.s133172

  日期：——

  Given the important role that inhibitory kappa B (IκB) kinase β (IKKβ) plays in pancreatic cancer (PC) development and progression, inhibitors targeting IKKβ are believed to be increasingly popular as novel anti-PC therapies. Two synthetic molecules, named EF24 and EF31, exhibited favorable potential in terms of inhibition of both IKKβ activity and PC cell proliferation. Aiming to enhance their cellular

  鉴于抑制性κB（IκB）激酶β（IKKβ）在胰腺癌（PC）的发展和进程中发挥着重要作用，人们认为靶向IKKβ的抑制剂作为新型抗PC疗法越来越受欢迎。就抑制IKKβ活性和PC细胞增殖而言，两种名为EF24和EF31的合成分子表现出有利的潜力。为了增强它们的细胞效力并分析它们的结构-活性关系，设计并合成了四个系列的EF24和EF31类似物。通过激酶活性和癌细胞的活力筛选，D6对IKKβ活性和PC细胞增殖均表现出出色的抑制作用。此外，多项生物学评估表明，D6直接与IKKβ结合，并显着抑制肿瘤坏死因子-α诱导的IKKβ/核因子κB通路的激活，并有效诱导癌细胞凋亡。此外，分子对接和分子动力学模拟分析表明，D6和IKKβ之间的主导力包括疏水相互作用。总之，D6可能是PC治疗的有前途的治疗剂，它也为新型IKKβ抑制剂的设计提供了结构上的线索。
• Domino Multicomponent Approach for the Synthesis of Functionalized Spiro-Indeno[1,2-b]quinoxaline Heterocyclic Hybrids and Their Antimicrobial Activity, Synergistic Effect and Molecular Docking Simulation
  作者：Abdulrahman I. Almansour、Natarajan Arumugam、Raju Suresh Kumar、Dhaifallah M. Al-thamili、Govindasami Periyasami、Karuppiah Ponmurugan、Naif Abdullah Al-Dhabi、Karthikeyan Perumal、Dhanaraj Premnath

  DOI：10.3390/molecules24101962

  日期：——

  dispiropyrrolidine tethered N-styrylpiperidone hybrid heterocycles in moderate to good yield in a single step. These compounds were evaluated for their antimicrobial activity against bacterial and fungal pathogens, therein compounds 8f, 8h, and 8l displayed significant activity against tested microbial pathogens. The synergistic effect revealed that the combination of compound 8h with streptomycin and vancomycin

  通过多米诺多组分 1,3-偶极环加成策略，使用离子液体中的新型偶氮甲碱叶立德，开发了一种迄今为止尚未探索的新型杂环化合物的便利合成，包括二螺吡咯烷、N-苯乙烯基哌啶酮和茚并 [1,2-b] 喹喔啉单元， 1-丁基-3-甲基咪唑鎓溴化物。该多米诺协议涉及 1,3-偶极环加成和伴随的烯胺反应，在一个步骤中以中等至良好的产率提供二螺吡咯烷系留的 N-苯乙烯基哌啶酮杂环。评估了这些化合物对细菌和真菌病原体的抗微生物活性，其中化合物 8f、8h 和 8l 对测试的微生物病原体显示出显着的活性。
• Dipolar cycloaddition based multi-component reaction: Synthesis of spiro tethered acenaphthylene–indolizine–pyridinone hybrids
  作者：Raju Suresh Kumar、Abdulrahman I. Almansour、Natarajan Arumugam、Govindasami Periyasami、S. Athimoolam、Raju Ranjith Kumar、Mohammad Asad、Abdullah M. Asiri

  DOI：10.1016/j.tetlet.2018.07.051

  日期：2018.8

  novel dispiro acenaphthylene–indolizine–pyridinone hybrid heterocycles have been achieved through one-pot four-component domino 1,3-dipolar cycloaddition–Michael addition–air oxidation sequence of reactions.

  通过一锅四组分多米诺1，3-偶极环加成反应-迈克尔加成反应-空气氧化反应序列，实现了新型二螺o基-吲哚嗪-吡啶酮杂合杂环的立体选择性合成。
• Functionalized spirooxindole-indolizine hybrids: Stereoselective green synthesis and evaluation of anti-inflammatory effect involving TNF-α and nitrite inhibition
  作者：Raju Suresh Kumar、Paulrayer Antonisamy、Abdulrahman I. Almansour、Natarajan Arumugam、Govindasami Periyasami、Mohammad Altaf、Ha-Rim Kim、Kang-Beom Kwon

  DOI：10.1016/j.ejmech.2018.04.060

  日期：2018.5

  Stereoselective synthesis of a small library of novel spiroheterocyclic hybrids including indolizine, oxindole, and substituted piperidine units has been accomplished in [bmim]Br using a [3 + 2] cycloaddition strategy in good yield and were tested for their anti-inflammatory activities. The effects of compounds (4a-o) against inflammation were studied using carrageenan-induced hind paw oedema, croton

  使用[3 + 2]环加成策略，在[bmim] Br中完成了一个新颖的螺杂环混合物（包括吲哚利嗪，羟吲哚和取代的哌啶单元）的小型文库的立体选择性合成，并获得了良好的收率，并对其抗炎活性进行了测试。使用角叉菜胶诱导的后足水肿，巴豆油诱导的耳部水肿和棉丸诱导的肉芽肿模型研究了化合物（4a-o）对炎症的影响。在杂环杂种中，化合物4d，4g和4o对急性和慢性炎症模型表现出显着的抗炎活性。这些化合物在角叉菜胶诱导的后爪水肿中也显示出对PGE2，TNF-α和亚硝酸盐水平的显着抑制作用。因此，从我们的研究中可以明显看出，这些新型螺杂环杂种4d，4g，