4-benzylidene-2-p-tolyloxazol-5(4H)-one

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-benzylidene-2-p-tolyloxazol-5(4H)-one
• 英文别名: 2-(p-Tolyl)-4-benzyliden-oxazolinon-(5)；2-p-Tolyl-4-benzylidenoxazol-5-on；4-Benzyliden-2-p-tolyloxazol-5-on；4-benzylidene-2-(4-methylphenyl)-1,3-oxazol-5(4H)-one；4-benzylidene-2-p-tolyl-4H-oxazol-5-one；NSC 117533；4-Benzylidene-2-(4-methylphenyl)-1,3-oxazol-5-one
• 化学式: C₁₇H₁₃NO₂
• mdl: MFCD00428561
• 分子量: 263.296
• InChiKey: CQBYEKYOZUQQPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-benzylidene-2-p-tolyloxazol-5(4H)-one 在 磺酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 N-[(Z)-2-chloro-2-phenyl-1-(piperidine-1-carbonyl)vinyl]-4-methyl-benzamide
  参考文献：
  名称：

  Synthesis and Quantitative Structure-activity Relationships Study for Arylpropenamide Derivatives as Inhibitors of Hepatitis B Virus Replication

  摘要：

  A series of new arylpropenamide derivatives containing different aryl groups were synthesized, characterized, and evaluated for their anti‐hepatitis B virus (HBV) activities. A new high accuracy QSAR model of arylpropenamide was constructed based on a more completely activities data and calculation parameter. The 2D‐QSAR equations, by using DFT and multiple linear regression analysis methods, revealed that higher value of thermal energy (TE) and lower entropy (Sө) increase the anti‐HBV activities of the arylpropenamide molecules. Predictive 3D‐QSAR models were established by SYBYL multifit molecular alignment rule. The optimum models were all statistically significant with cross‐validated and conventional coefficients, indicating that they were reliable enough for activity prediction.

  DOI：

  10.1111/cbdd.12774
• 作为产物：
  描述：

  对甲基苯甲酰氯 在 sodium acetate 、 乙酸酐 、 sodium hydroxide 作用下， 以 水 为溶剂， 生成 4-benzylidene-2-p-tolyloxazol-5(4H)-one
  参考文献：
  名称：

  Phenylpropenamide derivatives: Anti-hepatitis B virus activity of the Z isomer, SAR and the search for novel analogs

  摘要：

  Phenylpropenamides have been reported to be a class of non-nucleoside inhibitors of the hepatitis B virus (HBV). This class of compounds was explored with the objective of developing potent anti-HBV agents, with a novel mechanism of action, that could be combined with nucleos(t) ide analogs currently used to treat HBV infection. To accomplish this objective a series of substituted arylpropenamide derivatives were prepared and the E and Z geometrical isomers were separated. The structural identity of each of the E and Z isomers was determined by single crystal X-ray crystallography. Contrary to previous reports, the activity of this class of molecules resides in the Z isomer. Further structure-activity relationship studies around the active Z isomer identified compounds that displayed potent antiviral activity against HBV with EC90 value of approximately 0.5 mu M in vitro. Attempts to develop ring constrained analogs did not lead to active HBV inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.077

文献信息

• 5(4<i>H</i>)-Oxazolones as Novel Antitubercular Agents: Synthesis, Characterisation and Structure Activity Study
  作者：K. P. Suhasini、Praveen K. Chintakindi、K. Chaguruswamy、Y. L. N. Murthy

  DOI：10.1002/jccs.201500111

  日期：2015.10

  In search of novel anti tubercular agents, a series of twelve 4‐(substituted benzylidene)‐2‐p‐tolyloxazol‐5(4H)‐ones (5a–5l) has been synthesized, characterised and subjected to evaluate their antitubercular activity for the first time against Mycobacterium tuberculosis H37Rv (ATCC 27294). The out‐put of these studies disclosed that all the synthesized target molecules of the series displayed good

  为寻找新型抗结核药，已合成了一系列十二种4-（取代的亚苄基）-2-对甲苯甲唑-5（4 H）-酮（5a - 5l），并对其特性进行了评估。首次抗结核分枝杆菌H37Rv（ATCC 27294）。这些研究的结果表明，与标准一线抗结核药物利福平和异烟肼相比，该系列所有合成的靶分子均显示出良好至中等的活性，MIC值为2–32μg/ mL。化合物5e具有三个相互之间甲氧基的甲氧基，是该系列中最独特的化合物，因为它具有出色的体外抗结核活性，因此可以作为有希望的进一步探索的先导分子。
• Synthesis and evaluation of new phenyl acrylamide derivatives as potent non-nucleoside anti-HBV agents
  作者：Xiaoke Gu、Yinpeng Zhang、Yueting Zou、Xin Li、Mingyu Guan、Qingqing Zhou、Jingying Qiu

  DOI：10.1016/j.bmc.2020.115892

  日期：2021.1

  As a continuation of our previous work, a series of new phenyl acrylamide derivatives (4Aa-g, 4Ba-t, 5 and 6a-c) were designed and synthesized as non-nucleoside anti-HBV agents. Among them, compound 4Bs could potently inhibit HBV DNA replication in wild-type and lamivudine (3TC)/entecavir resistant HBV mutant strains with IC50 values of 0.19 and 0.18 μM, respectively. Notably, the selective index value

  作为我们先前工作的延续，设计并合成了一系列新的苯基丙烯酰胺衍生物（4Aa-g，4Ba-t，5和6a-c）作为非核苷类抗HBV剂。其中，化合物4Bs可以有效抑制野生型和拉米夫定（3TC）/恩替卡韦耐药HBV突变株中HBV DNA复制，IC 50值分别为0.19和0.18μM。值得注意的是，4Bs的选择性指数值高于526，表明安全性良好。有趣的是，不像核苷类似物3TC，4BS能显著禁止3.5kb的pgRNA表达。分子对接研究表明4B通过疏水，π-π和H键相互作用可以很好地适合HBV核心蛋白的二聚体-二聚体界面。考虑到强效的抗HBV活性，低毒性以及与核苷类抗HBV药物3TC不同的抗HBV机理，化合物4Bs有望成为开发新型非核苷类抗HBV治疗药物的有希望的线索，并值得进一步研究。
• Design, synthesis, and biological evaluation of novel 1,2-diaryl-4-substituted-benzylidene-5(4<i>H</i> )-imidazolone derivatives as cytotoxic agents and COX-2/LOX inhibitors
  作者：Phoebe F. Lamie、John N. Philoppes、Lucie Rárová

  DOI：10.1002/ardp.201700311

  日期：2018.4

  ‐imidazolone derivatives 4a–l was synthesized. Their structures were confirmed by different spectroscopic techniques (IR, 1H NMR, DEPT‐Q NMR, and mass spectroscopy) and elemental analyses. Their cytotoxic activities in vitro were evaluated against breast, ovarian, and liver cancer cell lines and also normal human skin fibroblasts. Cyclooxygenase (COX)‐1, COX‐2 and lipoxygenase (LOX) inhibitory activities

  合成了一系列新的 1,2-二芳基-4-取代-亚苄基-5(4H)-咪唑酮衍生物 4a-l。它们的结构通过不同的光谱技术（红外、1H 核磁共振、DEPT-Q 核磁共振和质谱）和元素分析得到证实。它们在体外对乳腺癌、卵巢癌和肝癌细胞系以及正常人皮肤成纤维细胞的细胞毒活性进行了评估。测量了环氧化酶 (COX)-1、COX-2 和脂氧化酶 (LOX) 抑制活性。合成的化合物显示出对 COX-2 而不是 COX-1 的选择性，IC50 值（0.25-1.7 µM）低于吲哚美辛（IC50 = 9.47 µM），略高于塞来昔布（IC50 = 0.071 µM） . 恶唑衍生物 4e (SI = 3.67) 对 COX-2 的选择性指数几乎等于塞来昔布 (SI = 3.66)。对于 LOX 抑制活性，新化合物的 IC50 值为 0.02–74.03 µM，而参考齐留通的 IC50 值为 0.83 µM。发现活性最强的化合物
• Nickel‐Catalyzed Asymmetric Hydrogenation of 2‐Amidoacrylates
  作者：Yawen Hu、Jianzhong Chen、Bowen Li、Zhenfeng Zhang、Ilya D. Gridnev、Wanbin Zhang

  DOI：10.1002/anie.201916534

  日期：2020.3.23

  chiral bisphosphine ligand, was found to be an efficient catalyst for the asymmetric hydrogenation of 2-amidoacrylates, affording the chiral α-amino acid esters in quantitative yields and excellent enantioselectivity (up to 96 % ee). The active catalyst component was studied by NMR and HRMS, which helped us to realize high catalytic efficiency on a gram scale with a low catalyst loading (S/C=2000).

  发现富含地球的镍与合适的手性双膦配体配合使用，是2-酰胺基丙烯酸酯不对称氢化的有效催化剂，以定量收率和优异的对映选择性（高达96％ee）提供了手性α-氨基酸酯。通过NMR和HRMS对活性催化剂组分进行了研究，这有助于我们以克级实现高催化效率且催化剂负载量低（S / C = 2000）。氢化产物可以简单地转化为手性α-氨基酸，β-氨基醇及其生物活性衍生物。此外，使用氘标记实验和计算计算研究了催化机理。
• Catalytic aza-Wittig Reaction of Acid Anhydride for the Synthesis of 4<i>H</i>-Benzo[<i>d</i>][1,3]oxazin-4-ones and 4-Benzylidene-2-aryloxazol-5(4<i>H</i>)-ones
  作者：Long Wang、Yi-Bi Xie、Nian-Yu Huang、Jia-Ying Yan、Wei-Min Hu、Ming-Guo Liu、Ming-Wu Ding

  DOI：10.1021/acscatal.6b00165

  日期：2016.6.3

  copper-catalyzed reduction of phosphine oxide was used and found effective for this transformation. Additionally, the one-pot catalytic aza-Wittig reaction of carboxylic acids was achieved. Furthermore, NMR experiments and Hammett plot recorded the process of catalytic aza-Wittig reaction of anhydride, which provides direct proof that the copper-catalyzed reduction of waste phosphine oxide is the key step

  与醛，酮，酰胺和酯的aza-Wittig反应相比，酸酐的aza-Wittig反应总是被忽略，这应该是Wittig反应的重要组成部分。在这里，酸酐的aza-Wittig反应和酸酐的aza-Wittig催化反应均以高收率开发，这为合成4 H-苯并[ d ] [1,3]恶嗪-4-酮和4-亚苄基-2-芳基恶唑-5（4 H）-那些。使用了铜催化的氧化膦还原的策略，发现该策略对这种转化有效。另外，实现了羧酸的一锅催化的氮杂-维蒂希反应。此外，NMR实验和Hammett曲线记录了酸酐的催化氮杂-维蒂希反应过程，这直接证明了铜催化的废氧化膦的还原是该转化过程中的关键步骤。