3,5-bis(2-methylbenzylidene)piperidin-4-one | 1314761-68-6

• 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-methylbenzylidene)piperidin-4-one
• CAS: 1314761-68-6
• 化学式: C₂₁H₂₁NO
• 分子量: 303.404
• InChiKey: HGBAWYFKDXSOPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.94
• 重原子数：
  23.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  29.1
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  3,5-bis(2-methylbenzylidene)piperidin-4-one 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-methylphenylmethylidene)tetrahydro-4"-(1H)-pyridinone-4-(2-methylphenyl)-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：

  4-氧代哌啶酮盐酸盐 、 2-甲基苯甲醛 在 盐酸 、 potassium carbonate 、 溶剂黄146 作用下， 以 水 、 丙酮 为溶剂， 反应 24.0h， 生成 3,5-bis(2-methylbenzylidene)piperidin-4-one
  参考文献：
  名称：

  一锅三组分合成及高官能化螺吲哚-吡咯烷杂环杂化物体外抗癌活性研究

  摘要：

  为了开发具有独特作用机制的更有效且价格合理的抗癌剂，我们通过一锅三组分 (3+2) 环加成策略以良好的收率设计并合成了螺羟吲哚-吡咯烷杂环杂化物的衍生物。利用傅立叶变换红外光谱、核磁共振光谱和质谱对合成化合物的理化性质进行了彻底的表征。此外，还评估了这些化合物对浓度高达 200 µg/mL 的 HepG2 细胞的抗癌活性的影响。对高活性分子支架进行了深入的机理研究，发现细胞死亡的主要途径是细胞凋亡，细胞凋亡是通过诱导活性氧并随后参与半胱天冬酶而发生的。

  DOI：

  10.3390/molecules25235581

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。
• 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。
• 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，
• Microwave assisted synthesis, cholinesterase enzymes inhibitory activities and molecular docking studies of new pyridopyrimidine derivatives
  作者：Alireza Basiri、Vikneswaran Murugaiyah、Hasnah Osman、Raju Suresh Kumar、Yalda Kia、Mohamed Ashraf Ali

  DOI：10.1016/j.bmc.2013.03.058

  日期：2013.6

  A series of hitherto unreported pyrido-pyrimidine-2-ones/pyrimidine-2-thiones were synthesized under microwave assisted solvent free reaction conditions in excellent yields and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibitory activity. Among the pyridopyrimidine derivatives, 7e and 7l displayed 2.5- and 1.5-fold higher enzyme inhibitory activities against AChE as compared to standard drug, galanthamine, with IC50 of 0.80 and 1.37 mu M, respectively. Interestingly, all the compounds except 6k, 7j and 7k displayed higher inhibitory potential against BChE enzyme in comparison to standard with IC50 ranging from 1.18 to 18.90 mu M. Molecular modeling simulations of 7e and 7l was performed using three-dimensional structure of Torpedo californica AChE (TcAChE) and human butyrylcholinesterase (hBChE) enzymes to disclose binding interaction and orientation of these molecule into the active site gorge of respective receptors. (C) 2013 Elsevier Ltd. All rights reserved.
• Dispiropyrrolidine tethered piperidone heterocyclic hybrids with broad-spectrum antifungal activity against Candida albicans and Cryptococcus neoformans
  作者：Sarah Lawson、Natarajan Arumugam、Abdulrahman I. Almansour、Raju Suresh Kumar、Shankar Thangamani

  DOI：10.1016/j.bioorg.2020.103865

  日期：2020.7

  Invasive fungal infections along with rising incidence of resistance to antifungal drugs pose increasing threat to immunocompromised individuals, including cancer patients. In this study, we examined the antifungal activity of dispiropyrrolidine tethered piperidone heterocyclic hybrids. Results indicate that compounds 5a and 6i have demonstrated a potent antifungal effect on multiple fungal strains, including Candida albicans, without exhibiting cytotoxicity to mammalian cells. Furthermore, these two compounds exhibited significant inhibition on Candida albicans hyphae and biofilm development that surpasses the FDA-approved antifungal drug currently used for treatment. Taken together, our results suggest that 5a and 6i are promising candidates for development into new antifungal drugs.