4-(4-(4-chlorophenyl)piperazin-1-yl)benzaldehyde

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(4-(4-chlorophenyl)piperazin-1-yl)benzaldehyde
• 英文别名: 4-[4-(4-chlorophenyl)piperazin-1-yl]benzaldehyde
• 化学式: C₁₇H₁₇ClN₂O
• 分子量: 300.788
• InChiKey: IYECFJSHPMSGDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  丙二酸 、 4-(4-(4-chlorophenyl)piperazin-1-yl)benzaldehyde 在 哌啶 、 吡啶 作用下， 反应 4.0h， 以95%的产率得到(E)-3-(4-(4-(4-chlorophenyl)piperazin-1-yl)phenyl)acrylic acid
  参考文献：
  名称：

  Design, synthesis, 3D pharmacophore, QSAR, and docking studies of carboxylic acid derivatives as Histone Deacetylase inhibitors and cytotoxic agents

  摘要：

  In this study, five series of (E)-6-(4-substituted phenyl)-4-oxohex-5-enoic acids IIb-f (E), (E)-3-(4-(substituted)-phenyl) acrylic acids IIIa-g (E), 4-(4-(substituted) phenylamino)-4-oxobutanoic acids VIa,b,e, 5-(4-(substituted) phenylamino)-5-oxopentanoic acids VIIa,f and 2-[(4-(substituted) phenyl) carbamoyl] benzoic acids VIIIa,e were designed and synthesized. Selected compounds were screened in vitro for their cytotoxic effect on 60 human NCI tumor cell lines. Compound IIf (E) displayed significant inhibitory activity against NCI Non-Small Cell Lung A549/ATCC Cancer cell line (68% inhibition) and NCI-H460 Cancer cell line (66% inhibition). Moreover, the final compounds were evaluated in vitro for their cytotoxic activity on HepG2 Cancer cell line in which histone deacetylase (HDAC) is overexpressed. Compounds IIc (E), IIf (E), IIIb (E), and IIIg (E) exhibited the highest cytotoxic activity against HepG2 human cancer cell lines with IC50 ranging from 2.27 to 10.71 mu M. In addition, selected compounds were tested on histone deacetylase isoforms (HDAC1-11). Molecular docking simulation was also carried out for HDLP enzyme to investigate their HDAC binding affinity. In addition, generation of 3D-pharmacophore model and quantitative structure activity relationship (QSAR) models were combined to explore the structural requirements controlling the observed cytotoxic properties. (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2014.08.006
• 作为产物：
  描述：

  1-(4-氯苯基)哌嗪 、 对氟苯甲醛 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以85%的产率得到4-(4-(4-chlorophenyl)piperazin-1-yl)benzaldehyde
  参考文献：
  名称：

  设计，合成和评估新型茚满二酮衍生物作为多功能药物，具有抑制胆碱酯酶，抗β-淀粉样蛋白聚集，抗阿尔茨海默氏病和神经保护的特性

  摘要：

  设计，合成和评价了一系列新型的2-（4-（4-取代的哌嗪-1-基）亚苄基）-1 H-茚-1,3（2 H）-二酮作为多功能抗阿尔茨海默病药物。化合物27 – 38的体外研究表明，这些化合物具有中等至极好的AChE，BuChE和Aβ聚集抑制活性。值得注意的是，化合物34和38在整个系列中是最具活性的多功能剂，并且对AChE表现出优异的抑制作用（IC 50  = 0.048μM：34 ; 0.036μM：38），Aβ聚集（最大抑制百分比为82.2％，IC 50  = 9.2） μM：34; 最大抑制百分比为80.9％，IC 50  = 10.11μM：38），并且在ORAC-FL分析中显示出显着的抗氧化潜能。两种化合物还成功减少了SH-SY5Y细胞中H 2 O 2诱导的氧化应激。令人着迷的是，化合物34和38在SH-SY5Y细胞中对H 2 O 2和Aβ诱导的毒性表现出了令人钦佩的神经保护作用。另

  DOI：

  10.1016/j.bmc.2016.06.027

文献信息

• Design, synthesis and evaluation of novel indandione derivatives as multifunctional agents with cholinesterase inhibition, anti-β-amyloid aggregation, antioxidant and neuroprotection properties against Alzheimer’s disease
  作者：Chandra Bhushan Mishra、Apra Manral、Shikha Kumari、Vikas Saini、Manisha Tiwari

  DOI：10.1016/j.bmc.2016.06.027

  日期：2016.8

  A series of novel 2-(4-(4-substituted piperazin-1-yl)benzylidene)-1H-indene-1,3(2H)-diones were designed, synthesized and appraised as multifunctional anti-Alzheimer agents. In vitro studies of compounds 27–38 showed that these compounds exhibit moderate to excellent AChE, BuChE and Aβ aggregation inhibitory activity. Notably, compounds 34 and 38 appeared as most active multifunctional agents in the

  设计，合成和评价了一系列新型的2-（4-（4-取代的哌嗪-1-基）亚苄基）-1 H-茚-1,3（2 H）-二酮作为多功能抗阿尔茨海默病药物。化合物27 – 38的体外研究表明，这些化合物具有中等至极好的AChE，BuChE和Aβ聚集抑制活性。值得注意的是，化合物34和38在整个系列中是最具活性的多功能剂，并且对AChE表现出优异的抑制作用（IC 50  = 0.048μM：34 ; 0.036μM：38），Aβ聚集（最大抑制百分比为82.2％，IC 50  = 9.2） μM：34; 最大抑制百分比为80.9％，IC 50  = 10.11μM：38），并且在ORAC-FL分析中显示出显着的抗氧化潜能。两种化合物还成功减少了SH-SY5Y细胞中H 2 O 2诱导的氧化应激。令人着迷的是，化合物34和38在SH-SY5Y细胞中对H 2 O 2和Aβ诱导的毒性表现出了令人钦佩的神经保护作用。另
• Design, synthesis, in silico and biological evaluation of novel 2-(4-(4-substituted piperazin-1-yl)benzylidene)hydrazine carboxamides
  作者：Shikha Kumari、Chandra Bhushan Mishra、Danish Idrees、Amresh Prakash、Rajesh Yadav、Md. Imtaiyaz Hassan、Manisha Tiwari

  DOI：10.1007/s11030-016-9714-7

  日期：2017.2

  A series of novel 2-(4-(4-substituted piperazin-1-yl)benzylidene)hydrazinecarboxamide derivatives has been successfully designed and synthesized to evaluate their potential as carbonic anhydrase (CA) inhibitors. The inhibitory potential of synthesized compounds against human CAI and CAII was evaluated. Compounds 3a–n exhibited \(\hbox IC}_50}\) values between \(1.89-}415.1\,\upmu \hbox M}\) against

  已经成功设计并合成了一系列新型的2-（4-（4-取代的哌嗪-1-基）亚苄基）肼甲酰胺衍生物，以评估其作为碳酸酐酶（CA）抑制剂的潜力。评估了合成化合物对人CAI和CAII的抑制潜力。化合物3A-N显示出\（\ hbox中IC} _ 50} \）之间的值\（1.89 - } 415.1 \，\ upmu \ hbox中M} \）对CAI和\（0.62 - } 66.9 \， \ upmu \ hbox M} \）针对CAII。化合物3g是活性最高的抑制剂，对CAII的\（\ hbox IC} _ 50} \）值为\（0.62 \，\ upmu \ hbox M} \）。化合物3g的分子对接研究带有CAII的化合物显示该化合物非常适合CAII的活性位点，并且与锌离子（\（\ hbox Zn} ^ 2 +} \））以及活性位点上的三个组氨酸残基相互作用。与CAII配合的
• Design, synthesis, in-silico and biological evaluation of novel donepezil derivatives as multi-target-directed ligands for the treatment of Alzheimer's disease
  作者：Chandra Bhushan Mishra、Shikha Kumari、Apra Manral、Amresh Prakash、Vikas Saini、Andrew M. Lynn、Manisha Tiwari

  DOI：10.1016/j.ejmech.2016.09.057

  日期：2017.1

  antioxidant activity. Among the entire series compounds IP-9, IP-13 and IP-15 appeared as most active multi-functional agents and displayed marked AChE inhibitory, Aβ disaggregation and antioxidant activity. Studies indicate that IP-13 and IP-15 showed better AChE inhibitory activity than the standard drug donepezil and IP-9, IP-13 as well as IP-15 exhibited better Aβ aggregation inhibitory activity than

  一种基于多奈哌齐的新型多功能剂“（E）-5,6-二甲氧基-2-（4-（4-取代的哌嗪-1-基）亚苄基）-2,3-二氢-1 H-茚满-已经设计并合成了“ 1-ones”作为潜在的抗阿尔茨海默氏病药物。体外研究表明，这些化合物显示出中等至良好的AChE和Aβ聚集抑制活性。这些衍生物还具有令人赞叹的抗氧化活性。在整个系列化合物中，IP-9，IP-13和IP-15是最活跃的多功能剂，并显示出显着的AChE抑制，Aβ分解和抗氧化活性。研究表明IP-13和IP-15表现出比标准药物多奈哌齐更好的AChE抑制活性，IP-9，IP-13和IP-15表现出比姜黄素更好的Aβ聚集抑制活性。这些化合物（IP-9，IP-13和IP-15）成功地减轻了H 2 O 2诱导的SH-SY5Y细胞的氧化应激，并表现出出色的针对H 2 O 2的神经保护活性。以及Aβ以浓度依赖性方式诱导SH-SY5Y细胞的毒性。而且，在细胞毒
• Design, synthesis, 3D pharmacophore, QSAR, and docking studies of carboxylic acid derivatives as Histone Deacetylase inhibitors and cytotoxic agents
  作者：Mona M. Abdel-Atty、Nahla A. Farag、Shaymaa E. Kassab、Rabah A.T. Serya、Khaled A.M. Abouzid

  DOI：10.1016/j.bioorg.2014.08.006

  日期：2014.12

  In this study, five series of (E)-6-(4-substituted phenyl)-4-oxohex-5-enoic acids IIb-f (E), (E)-3-(4-(substituted)-phenyl) acrylic acids IIIa-g (E), 4-(4-(substituted) phenylamino)-4-oxobutanoic acids VIa,b,e, 5-(4-(substituted) phenylamino)-5-oxopentanoic acids VIIa,f and 2-[(4-(substituted) phenyl) carbamoyl] benzoic acids VIIIa,e were designed and synthesized. Selected compounds were screened in vitro for their cytotoxic effect on 60 human NCI tumor cell lines. Compound IIf (E) displayed significant inhibitory activity against NCI Non-Small Cell Lung A549/ATCC Cancer cell line (68% inhibition) and NCI-H460 Cancer cell line (66% inhibition). Moreover, the final compounds were evaluated in vitro for their cytotoxic activity on HepG2 Cancer cell line in which histone deacetylase (HDAC) is overexpressed. Compounds IIc (E), IIf (E), IIIb (E), and IIIg (E) exhibited the highest cytotoxic activity against HepG2 human cancer cell lines with IC50 ranging from 2.27 to 10.71 mu M. In addition, selected compounds were tested on histone deacetylase isoforms (HDAC1-11). Molecular docking simulation was also carried out for HDLP enzyme to investigate their HDAC binding affinity. In addition, generation of 3D-pharmacophore model and quantitative structure activity relationship (QSAR) models were combined to explore the structural requirements controlling the observed cytotoxic properties. (C) 2014 Elsevier Inc. All rights reserved.
• Novel benzimidazole-acrylonitrile hybrids and their derivatives: Design, synthesis and antimycobacterial activity
  作者：Mustafa Mert Sirim、Vagolu Siva Krishna、Dharmarajan Sriram、Oya Unsal Tan

  DOI：10.1016/j.ejmech.2019.112010

  日期：2020.2

  This paper reports the synthesis and evaluation of some benzimidazole-acrylonitrile hybrid derivatives for their in vitro antimycobacterial activities against Mycobacterium tuberculosis H37Rv. Among the derivatives studied, 3b was found to be the most active compound with MIC of 0.78 μg/mL against M. tuberculosis. This is a quite good activity compared with ethambutol (MIC = 1.56 μg/mL). Moreover,

  本文报道了一些苯并咪唑-丙烯腈杂化衍生物的合成及其对结核分枝杆菌H37Rv的体外抗分枝杆菌活性的评价。在研究的衍生物中，发现3b是最有效的化合物，对结核分枝杆菌的MIC为0.78μg/ mL。与乙胺丁醇（MIC = 1.56μg/ mL）相比，这是一个相当不错的活性。而且，3b显示休眠形式的分枝杆菌的细菌计数减少2.8 log倍，比一线药物异烟肼，环丙沙星，利福平和莫西沙星更有效。对活性和休眠形式的结核分枝杆菌3b都具有活性，可能是开发治疗结核病的新药的有用候选人。