3-(4-Chlorophenyl)-1-(4-ethoxyphenyl)prop-2-en-1-one | 57076-87-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 3-(4-Chlorophenyl)-1-(4-ethoxyphenyl)prop-2-en-1-one
• CAS: 57076-87-6
• 化学式: C₁₇H₁₅ClO₂
• 分子量: 286.758
• InChiKey: BHSGVFFDBSTANJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(4-Chlorophenyl)-1-(4-ethoxyphenyl)prop-2-en-1-one 在 一水合肼 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成 5-(4-chlorophenyl)-3-(4-ethoxyphenyl)-4,5-dihydro-1H-pyrazole
  参考文献：
  名称：

  Development of Halogenated Pyrazolines as Selective Monoamine Oxidase-B Inhibitors: Deciphering via Molecular Dynamics Approach

  摘要：

  卤族元素已被报道在抑制单胺氧化酶（MAO）中发挥重要作用，与中枢神经系统的多种认知功能有关。研究了吡唑啉/卤代吡唑啉对人类单胺氧化酶-A和-B的抑制活性。在吡唑啉的第五位苯环上的卤素取代显示出强大的MAO-B抑制作用。化合物3-(4-乙氧基苯基)-5-(4-氟苯基)-4,5-二氢-1H-吡唑（EH7）对MAO-B表现出最高的抑制活性，IC50值为0.063 µM。在EH7中，对MAO-B的作用效力依次增加为：-F > -Cl（EH6）> -Br（EH8）> -H（EH1）。大多数化合物对MAO-A的残留活性在10 µM时均> 50％，除了EH7和EH8（IC50分别为8.38和4.31 µM）。EH7表现出最高的选择性指数（SI）值为133.0，其次是EH6，> 55.8。EH7是MAO-B的可逆和竞争性抑制剂，在动力学和可逆性实验中的Ki值为0.034 ± 0.0067 µM。分子动力学研究表明，EH7在活性位点内具有良好的结合亲和力和运动运动，并具有高稳定性。通过MM-PBSA观察到，手性对EH7与MAO-B的整体结合影响较小。因此，EH7可用于开发用于治疗各种神经退行性疾病的前导分子。

  DOI：

  10.3390/molecules26113264
• 作为产物：
  描述：

  4-氯苯甲醛 、 4-乙氧基苯乙酮 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 生成 3-(4-Chlorophenyl)-1-(4-ethoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  4-乙氧基查耳酮对氧化还原酶/皮林抑制剂的分子对接和对乳腺癌/皮肤癌细胞系的细胞毒性评价

  摘要：

  背景：α，β不饱和丙烯酮衍生物的作用因其生物学重要性而吸引了化学家。试图通过分子对接研究揭示乳腺癌和皮肤癌细胞系之间的相互作用。 目的：该研究旨在合成和表征4-乙氧基查耳酮以测试乳腺癌和皮肤癌的靶标。 方法：合成了一系列从4-乙氧基苯乙酮和取代的芳香醛开始的查尔酮类似物，并进行了表征，并评估了它们对人乳腺癌（MDA-MB-231）和人转移性黑色素瘤（A-375）的体外抗癌活性。 MTT法检测细胞系。进行对接模拟以研究查尔酮骨架在与细胞色素P450家族氧化还原酶结合的乳腺癌靶标抑制剂和对皮肤癌的Pirin抑制靶标结合的靶标抑制剂活性位点上的药物-受体相互作用。 结果与讨论：进行细胞毒性评估后，观察到与两种细胞系的邻位和间位相比，对位取代的化合物显示出更好的结果。分子对接研究揭示了与选定的氧化还原酶和Pirin抑制靶标相互作用的不同类型。配体-蛋白质相互作用和形态变化通过分子动力学监测。 结论

  DOI：

  10.2174/1570180817666200129143803

文献信息

• Novel chalcones and 1,3,5-triphenyl-2-pyrazoline derivatives as antibacterial agents
  作者：Ponnurengam Malliappan Sivakumar、Suresh Ganesan、Prabhawathi Veluchamy、Mukesh Doble

  DOI：10.1111/j.1747-0285.2010.01020.x

  日期：2010.11

  Novel sixteen chalcones and thirteen 1,3,5‐triphenyl‐2‐pyrazolines were synthesized and characterized using FT‐IR, HR‐Mass, NMR (1H‐NMR, 13C‐NMR, 135 DEPT, 1H–1H CoSY and 1H and 13C CoSY) and XRD. These compounds were evaluated for their antibacterial activity against six micro‐organisms, namely Bacillus subtilis NCIM 2718, Staphylococcus aureus NCIM 5021, Salmonella typhi NCIM 2501, Enterobacter aerogenes NCIM 5139, Pseudomonas aeruginosa NCIM 5029, and Proteus vulgaris NCIM 2813 by twofold dilution method using resazurin as the indicator dye. In the case of chalcones, compounds with hydroxyl and bromo substitutions in the B‐ring favor activity and benzyloxy substitution irrespective of its position in the A‐ring. In the case of 1,3,5‐triphenyl‐2‐pyrazolines, chloro substitution in the A‐ring favors activity. Hydrophilic/lipophilic balance of the compounds plays a major role in their antibacterial activity.
• Synthesis of novel halogenated triarylpyrazoles as selective COX-2 inhibitors: Anti-inflammatory activity, histopatholgical profile and in-silico studies
  作者：Khaled R.A. Abdellatif、Eman K.A. Abdelall、Madlen B. Labib、Wael A.A. Fadaly、Taha H. Zidan

  DOI：10.1016/j.bioorg.2020.104418

  日期：2020.12

  A novel series of halogenated triarylpyrazoles 12a-l was designed and synthesized. All target compounds showed good in vitro COX-2 inhibitory activity (IC₅₀ = 0.043-0.17 µM) over COX-1 (IC₅₀ = 7.8 - 15.4 µM) relative to celecoxib (COX-1/IC₅₀ = 9.87, COX-2/IC₅₀ = 0.055), with acceptable selectivity index values (SI = 50.6-253.1). Also, they displayed moderate to potent in vivo anti-inflammatory activity (% edema inhibition = 16.9-87.9) comparable to celecoxib (% edema inhibition = 46.6-72.1) as standard drug. Three fluorinated pyrazoles 12a, 12g and 12j, exhibited superior anti-inflammatory activity at all time intervals (% edema inhibition = 42.1-87.9) with better gastric profile (UI = 1.25-2.5) than the traditional NSAID; indomethacin (UI = 14) and were close to the selective COX-2 inhibitor; celecoxib (UI = 1.75). In-silico docking and ADME studies of 12a, 12g and 12j supported the obtained biological data and pointed out their potential use for the development of bio-available, safe and potent anti-inflammatory drugs.
• Molecular Docking of 4-ethoxychalcones on Oxidoreductase/Pirin Inhibitors and Cytotoxic Evaluation on Breast/Skin Cancer Cell Lines
  作者：Kishori Ramachandra Harshitha、Balladka Kunhanna Sarojini、Badiadka Narayana、Anupam Glorious Lobo、Bhuvanesh Sukhlal Kalal

  DOI：10.2174/1570180817666200129143803

  日期：2020.10.12

  results compared to ortho and meta positions for both the cell lines. Molecular docking studies revealed different types of interactions with selected oxidoreductase and Pirin inhibiting targets. Ligand-protein interactions and morphological changes are monitored by molecular dynamics. Conclusion: The presence of electron-withdrawing and donating groups on ring B marginally affected IC50 and docking scores

  背景：α，β不饱和丙烯酮衍生物的作用因其生物学重要性而吸引了化学家。试图通过分子对接研究揭示乳腺癌和皮肤癌细胞系之间的相互作用。 目的：该研究旨在合成和表征4-乙氧基查耳酮以测试乳腺癌和皮肤癌的靶标。 方法：合成了一系列从4-乙氧基苯乙酮和取代的芳香醛开始的查尔酮类似物，并进行了表征，并评估了它们对人乳腺癌（MDA-MB-231）和人转移性黑色素瘤（A-375）的体外抗癌活性。 MTT法检测细胞系。进行对接模拟以研究查尔酮骨架在与细胞色素P450家族氧化还原酶结合的乳腺癌靶标抑制剂和对皮肤癌的Pirin抑制靶标结合的靶标抑制剂活性位点上的药物-受体相互作用。 结果与讨论：进行细胞毒性评估后，观察到与两种细胞系的邻位和间位相比，对位取代的化合物显示出更好的结果。分子对接研究揭示了与选定的氧化还原酶和Pirin抑制靶标相互作用的不同类型。配体-蛋白质相互作用和形态变化通过分子动力学监测。 结论
• Development of Halogenated Pyrazolines as Selective Monoamine Oxidase-B Inhibitors: Deciphering via Molecular Dynamics Approach
  作者：Aathira Sujathan Nair、Jong-Min Oh、Vishal Payyalot Koyiparambath、Sunil Kumar、Sachithra Thazhathuveedu Sudevan、Opeyemi Soremekun、Mahmoud E. Soliman、Ahmed Khames、Mohamed A. Abdelgawad、Leena K. Pappachen、Bijo Mathew、Hoon Kim

  DOI：10.3390/molecules26113264

  日期：——

  Halogens have been reported to play a major role in the inhibition of monoamine oxidase (MAO), relating to diverse cognitive functions of the central nervous system. Pyrazoline/halogenated pyrazolines were investigated for their inhibitory activities against human monoamine oxidase-A and -B. Halogen substitutions on the phenyl ring located at the fifth position of pyrazoline showed potent MAO-B inhibition. Compound 3-(4-ethoxyphenyl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole (EH7) showed the highest potency against MAO-B with an IC50 value of 0.063 µM. The potencies against MAO-B were increased in the order of –F (in EH7) > –Cl (EH6) > –Br (EH8) > –H (EH1). The residual activities of most compounds for MAO-A were > 50% at 10 µM, except for EH7 and EH8 (IC50 = 8.38 and 4.31 µM, respectively). EH7 showed the highest selectivity index (SI) value of 133.0 for MAO-B, followed by EH6 at > 55.8. EH7 was a reversible and competitive inhibitor of MAO-B in kinetic and reversibility experiments with a Ki value of 0.034 ± 0.0067 µM. The molecular dynamics study documented that EH7 had a good binding affinity and motional movement within the active site with high stability. It was observed by MM-PBSA that the chirality had little effect on the overall binding of EH7 to MAO-B. Thus, EH7 can be employed for the development of lead molecules for the treatment of various neurodegenerative disorders.

  卤族元素已被报道在抑制单胺氧化酶（MAO）中发挥重要作用，与中枢神经系统的多种认知功能有关。研究了吡唑啉/卤代吡唑啉对人类单胺氧化酶-A和-B的抑制活性。在吡唑啉的第五位苯环上的卤素取代显示出强大的MAO-B抑制作用。化合物3-(4-乙氧基苯基)-5-(4-氟苯基)-4,5-二氢-1H-吡唑（EH7）对MAO-B表现出最高的抑制活性，IC50值为0.063 µM。在EH7中，对MAO-B的作用效力依次增加为：-F > -Cl（EH6）> -Br（EH8）> -H（EH1）。大多数化合物对MAO-A的残留活性在10 µM时均> 50％，除了EH7和EH8（IC50分别为8.38和4.31 µM）。EH7表现出最高的选择性指数（SI）值为133.0，其次是EH6，> 55.8。EH7是MAO-B的可逆和竞争性抑制剂，在动力学和可逆性实验中的Ki值为0.034 ± 0.0067 µM。分子动力学研究表明，EH7在活性位点内具有良好的结合亲和力和运动运动，并具有高稳定性。通过MM-PBSA观察到，手性对EH7与MAO-B的整体结合影响较小。因此，EH7可用于开发用于治疗各种神经退行性疾病的前导分子。