1-benzyl-3,5-bis-(4-dimethylamino-2-nitrobenzylidene)-piperidin-4-one | 1613453-00-1

• 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: 1-benzyl-3,5-bis-(4-dimethylamino-2-nitrobenzylidene)-piperidin-4-one
• 英文别名: 1-benzyl-3,5-bis(4-dimethylamino-2-nitrobenzylidene)piperidin-4-one
• CAS: 1613453-00-1
• 化学式: C₃₀H₃₁N₅O₅
• 分子量: 541.607
• InChiKey: RFESRTOEUQLFML-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.19
• 重原子数：
  40.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  113.07
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  N-苄基哌啶酮 、 4-二甲氨基-2-硝基苯甲醛 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以60%的产率得到1-benzyl-3,5-bis-(4-dimethylamino-2-nitrobenzylidene)-piperidin-4-one
  参考文献：
  名称：

  Synthesis of α, β-unsaturated carbonyl based compounds as acetylcholinesterase and butyrylcholinesterase inhibitors: Characterization, molecular modeling, QSAR studies and effect against amyloid β-induced cytotoxicity

  摘要：

  A series of novel carbonyl compounds was synthesized by a simple, eco-friendly and efficient method. These compounds were screened for anti-oxidant activity, in vitro cytotoxicity and for inhibitory activity for acetylcholinesterase and butyrylcholinesterase. The effect of these compounds against amyloid β-induced cytotoxicity was also investigated. Among them, compound 14 exhibited strong free radical scavenging activity (18.39 μM) while six compounds (1, 3, 4, 13, 14, and 19) were found to be the most protective against Aβ-induced neuronal cell death in PC12 cells. Compounds 4 and 14, containing N-methyl-4-piperidone linker, showed high acetylcholinesterase inhibitory activity as compared to reference drug donepezil. Molecular docking and QSAR (Quantitative Structure-Activity Relationship) studies were also carried out to determine the structural features that are responsible for the acetylcholinesterase and butyrylcholinesterase inhibitory activity.

  DOI：

  10.1016/j.ejmech.2014.06.034

文献信息

• Biological Activity and Molecular Docking Studies of Curcumin-Related α,β-Unsaturated Carbonyl-Based Synthetic Compounds as Anticancer Agents and Mushroom Tyrosinase Inhibitors
  作者：Syed Nasir Abbas Bukhari、Ibrahim Jantan、Oya Unsal Tan、Muhammad Sher、M. Naeem-ul-Hassan、Hua-Li Qin

  DOI：10.1021/jf501145b

  日期：2014.6.18

  Hyperpigmentation in human skin and enzymatic browning in fruits, which are caused by tyrosinase enzyme, are not desirable. Investigations in the discovery of tyrosinase enzyme inhibitors and search for improved cytotoxic agents continue to be an important line in drug discovery and development. In present work, a new series of 30 compounds bearing α,β-unsaturated carbonyl moiety was designed and synthesized following curcumin as model. All compounds were evaluated for their effects on human cancer cell lines and mushroom tyrosinase enzyme. Moreover, the structure-activity relationships of these compounds are also explained. Molecular modeling studies of these new compounds were carried out to explore interactions with tyrosinase enzyme. Synthetic curcumin-like compounds (2a-b) were identified as potent anticancer agents with 81-82% cytotoxicity. Five of these newly synthesized compounds (1a, 8a-b, 10a-b) emerged to be the potent inhibitors of mushroom tyrosinase, providing further insight into designing compounds useful in fields of food, health, and agriculture.
• Pharmacological evaluation and docking studies of α,β-unsaturated carbonyl based synthetic compounds as inhibitors of secretory phospholipase A2, cyclooxygenases, lipoxygenase and proinflammatory cytokines
  作者：Syed Nasir Abbas Bukhari、Gianluigi Lauro、Ibrahim Jantan、Giuseppe Bifulco、Muhammad Wahab Amjad

  DOI：10.1016/j.bmc.2014.05.052

  日期：2014.8

  Arachidonic acid and its metabolites have generated high level of interest among researchers due to their vital role in inflammation. The inhibition of enzymes involved in arachidonic acid metabolism has been considered as synergistic anti-inflammatory effect. A series of novel alpha,beta-unsaturated carbonyl based compounds were synthesized and evaluated for their inhibitory activity on secretory phospholipase A(2) (sPLA(2)), cyclooxygenases (COX), soybean lipoxygenase (LOX) in addition to proinflammatory cytokines comprising IL-6 and TNF-alpha. Six alpha,beta-unsaturated carbonyl based compounds (2, 3, 4, 12, 13 and 14) exhibited strong inhibition of sPLA(2) activity, with IC50 values in the range of 2.19-8.76 mu M. Nine compounds 1-4 and 10-14 displayed inhibition of COX-1 with IC50 values ranging from 0.37 to 1.77 mu M (lower than that of reference compound), whereas compounds 2, 10, 13 and 14 strongly inhibited the COX-2. The compounds 10-14 exhibited strong inhibitory activity against LOX enzyme. All compounds were evaluated for the inhibitory activities against LPS-induced TNF-alpha and IL-6 release in the macrophages. On the basis of screening results, five active compounds 3,4, 12,13 and 14 were found strong inhibitors of TNF-alpha and IL-6 release in a dose-dependent manner. Molecular docking experiments were performed to clarify the molecular aspects of the observed COX and LOX inhibitory activities of the investigated compounds. Present findings increases the possibility that these alpha,beta-unsaturated carbonyl based compounds might serve as beneficial starting point for the design and development of improved anti-inflammatory agents. (C) 2014 Elsevier Ltd. All rights reserved.
• Synthesis of α, β-unsaturated carbonyl based compounds as acetylcholinesterase and butyrylcholinesterase inhibitors: Characterization, molecular modeling, QSAR studies and effect against amyloid β-induced cytotoxicity
  作者：Syed Nasir Abbas Bukhari、Ibrahim Jantan、Vijay H. Masand、Devidas T. Mahajan、Muhammad Sher、M. Naeem-ul-Hassan、Muhammad Wahab Amjad

  DOI：10.1016/j.ejmech.2014.06.034

  日期：2014.8

  A series of novel carbonyl compounds was synthesized by a simple, eco-friendly and efficient method. These compounds were screened for anti-oxidant activity, in vitro cytotoxicity and for inhibitory activity for acetylcholinesterase and butyrylcholinesterase. The effect of these compounds against amyloid β-induced cytotoxicity was also investigated. Among them, compound 14 exhibited strong free radical scavenging activity (18.39 μM) while six compounds (1, 3, 4, 13, 14, and 19) were found to be the most protective against Aβ-induced neuronal cell death in PC12 cells. Compounds 4 and 14, containing N-methyl-4-piperidone linker, showed high acetylcholinesterase inhibitory activity as compared to reference drug donepezil. Molecular docking and QSAR (Quantitative Structure-Activity Relationship) studies were also carried out to determine the structural features that are responsible for the acetylcholinesterase and butyrylcholinesterase inhibitory activity.