N-benzyl-2-(4-formylphenoxy)acetamide | 552843-08-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-benzyl-2-(4-formylphenoxy)acetamide
• CAS: 552843-08-0
• 化学式: C₁₆H₁₅NO₃
• 分子量: 269.3
• InChiKey: JCPGPKCWIDFEEH-UHFFFAOYSA-N

物化性质

• 沸点：
  538.7±40.0 °C(Predicted)
• 密度：
  1.198±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  巴比妥酸 、 N-benzyl-2-(4-formylphenoxy)acetamide 以 乙醇 、 水 为溶剂， 以85.9%的产率得到N-benzyl-2-(4-((2,4,6-trioxotetrahydropyrimidin-5(6H)-ylidene)methyl)phenoxy)acetamide
  参考文献：
  名称：

  Synthesis and biological activity of novel barbituric and thiobarbituric acid derivatives against non-alcoholic fatty liver disease

  摘要：

  Forty-four barbituric acid or thiobarbituric acid derivatives were synthesized and evaluated for their effects on adipogenesis of 3T3-L1 adipocytes by measuring the expression of adiponectin in vitro. Four compounds (3a, 30, 3s, 4t) were found to increase the expression of adiponectin and lower the leptin level in 31341 adipocytes at respective concentration of 10 mu M. Among them, 3s showed the most efficacious. Oral administration of 3s effectively reduced body weight, liver weight, and visceral fat and regulated serum levels of biochemical markers in the high-fat/diet-induced Wistar rats. Histopathological evaluation of liver sections by Oil Red O and H&E staining confirmed 3s as a potent, orally active molecule for reducing fat deposition against non-alcoholic fatty liver disease. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.02.033
• 作为产物：
  描述：

  苄胺 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 13.0h， 生成 N-benzyl-2-(4-formylphenoxy)acetamide
  参考文献：
  名称：

  microRNA-155 (miR-155) 和 BACE1 抑制剂对唐氏综合症和阿尔茨海默病患者记忆的可能影响：设计、合成、虚拟筛选、分子建模和生物学评估

  摘要：

  摘要 MiR-155 在多种生理和病理机制中发挥主要作用，例如唐氏综合症 (DS)、免疫和炎症以及潜在的抗 AD 治疗靶点。miR-155 是 DS 患者中过表达的 miRNA 之一，直接和间接地促进了 DS 的发作或进展。由于 miR-155 可以在转录后水平同时减少几个基因的翻译，因此靶向 miR-155 可能为 DS 的治疗奠定基础。在这方面提供治疗干预的合理策略之一是设计和开发抑制 miR-155 功能或生物发生或成熟的新型小分子。在目前的研究中，我们的目标是通过采用计算药物设计方法以及体外研究，引入具有抑制选择性 miR-155 加工产生潜力的小分子化合物。我们设计并合成了一系列新的咪唑并[1,2-a]吡啶衍生物，作为治疗 AD 的新型非消化性候选药物。研究了设计的化合物在体外和细胞中的 BACE1 和 miR-155 结合剂抑制潜力。此外，我们提出了一种系统的计算方法，包括 3D

  DOI：

  10.1080/07391102.2021.1873861

文献信息

• Synthesis, glucose uptake activity and structure–activity relationships of some novel glitazones incorporated with glycine, aromatic and alicyclic amine moieties via two carbon acyl linker
  作者：B.R. Prashantha Kumar、Mukesh Soni、S. Santhosh Kumar、Kuldeep Singh、Mohan Patil、R.B. Nasir Baig、Laxmi Adhikary

  DOI：10.1016/j.ejmech.2010.12.019

  日期：2011.3

  Three series of novel glitazones were designed and prepared by using appropriate synthetic schemes to incorporate glycine, aromatic and alicyclic amines via two carbon linker. Compounds were synthesized both under conventional and microwave methods. Nineteen out of twenty four synthesized compounds were evaluated for their in vitro glucose uptake activity using isolated rat hemi-diaphragm. Compounds

  通过使用适当的合成方案，通过两个碳连接基掺入甘氨酸，芳香族和脂环族胺，设计和制备了三个系列的新型格列酮。化合物是在常规方法和微波方法下合成的。使用分离的大鼠半隔膜评估了二十四种合成化合物中的十九种的体外葡萄糖摄取活性。化合物，6，图9A，图13A，13B，13C，13F和13H显示出显著葡萄糖摄取活性。有关其合成和体外的插图 描述了葡萄糖摄取活性以及结构-活性关系。
• Studies on a Novel Safety-Catch Linker Cleaved by Pummerer Rearrangement¹
  作者：Chih-Ho Tai、Hsiao-Ching Wu、Wen-Ren Li

  DOI：10.1021/ol049120s

  日期：2004.8.1

  We describe the use of a sulfide linkage as a safety-catch linker. This linker is significantly stable to acidic as well as basic conditions and allows transformations to be carried out on solid supports. Moreover, its cleavage is facile by applying Pummerer rearrangement after transforming it to sulfoxide.

  我们描述了使用硫化物连接作为安全捕获连接子。该接头对酸性和碱性条件都非常稳定，并且可以在固体载体上进行转化。此外，通过将其转化为亚砜后进行Pummerer重排，其裂解是容易的。
• Strategy To Tether Organometallic Ruthenium−Arene Anticancer Compounds to Recombinant Human Serum Albumin
  作者：Wee Han Ang、Elisa Daldini、Lucienne Juillerat-Jeanneret、Paul J. Dyson

  DOI：10.1021/ic701474m

  日期：2007.10.1

  In order to utilize macromolecules for drug targeting and delivery, a strategy to tether organometallic ruthenium-arene drugs to carrier protein molecules was developed. The approach involves the design of a drug fragment capable of conjugating to linker molecules on a modified carrier protein via hydrazone bond formation. The proof-of-concept using recombinant human serum albumin is described.

  为了利用大分子进行药物靶向和递送，开发了将有机金属钌-芳烃药物束缚到载体蛋白分子的策略。该方法涉及能够通过fragment键形成与修饰的载体蛋白上的接头分子缀合的药物片段的设计。描述了使用重组人血清白蛋白的概念验证。
• Synthesis and Biological Evaluation of Novel 5-Benzylidenethiazolidine-2,4-dione Derivatives for the Treatment of Inflammatory Diseases
  作者：Liang Ma、Caifeng Xie、Yinghua Ma、Juan Liu、Mingli Xiang、Xia Ye、Hao Zheng、Zhizhi Chen、Qinyuan Xu、Tao Chen、Jinying Chen、Jincheng Yang、Neng Qiu、Guangcheng Wang、Xiaolin Liang、Aihua Peng、Shengyong Yang、Yuquan Wei、Lijuan Chen

  DOI：10.1021/jm1011534

  日期：2011.4.14

  Twenty-two compounds based on thiazolidine-2,4-dione moiety were synthesized and evaluated for the inhibitory potency on the production of nitric oxide (NO), inducible nitric oxide synthase (iNOS) activity, and the generation of prostaglandin E-2 (PEG(2)). (Z)-N-(3-Chlorophenyl)-2-(4-((2,4-dioxothiazolidin-5-ylidene) methyl) phenoxy) acetamide (3I), superior to the commercial anti-inflammatory drug indomethacin, significantly inhibited iNOS activity (IC50 = 8.66 mu M), iNOS-mediated NO, and cyclooxnenase (COX)-2-derived PGE(2) production (IC50 = 4.16 and 23.55 mu M, respectively) on lipopolysaccharide (LPS)-induced. RAW 264.7 cells. Docking study revealed that 3I was perfectly docking into the active site of murine iNOS and suppressed the expression of iNOS protein as evidenced by Western blot analysis. At the dose of 50 mg/kg, oral administration of 3I possessed protective properties in both carrageenan-induced paw edema and adjuvant-induced arthritis rat models.
• Cink4T, a quinazolinone-based dual inhibitor of Cdk4 and tubulin polymerization, identified via ligand-based virtual screening, for efficient anticancer therapy
  作者：Vinay Sonawane、Mohd Usman Mohd Siddique、Surender Singh Jadav、Barij Nayan Sinha、Venkatesan Jayaprakash、Bhabatosh Chaudhuri

  DOI：10.1016/j.ejmech.2019.01.011

  日期：2019.3

  Inhibition of cyclin dependent kinase 4 (Cdk4) prevents cancer cells from entering the early G(0)/G(1) phase of the cell division cycle whereas inhibiting tubulin polymerization blocks cancer cells' ability to undergo mitosis (M) late in the cell cycle. We had reported earlier that two non-planar and relatively non-toxic fascaplysin derivatives, an indole and a tryptoline, inhibit Cdk4 with IC50 values of 6.2 and 10 mu M, respectively. Serendipitously, we had also found that they inhibited tubulin polymerization. The molecules were efficacious in mouse tumor models. We have now identified Cink4T in a 59-compound quinazolinone library, designed on the basis of ligand-based virtual screening, as a compound that inhibits Cdk4 and tubulin. Its IC50 value for Cdk4 inhibition is 0.47 mu M and >50 mu M for inhibition of Cdk1, Cdk2, Cdk6, Cdk9. Cink4T inhibits tubulin polymerization with an IC50 of 0.6 mu M. Molecular modelling studies on Cink4T with Cdk4 and tubulin crystal structures lend support to these observations. Cancer cell cycle analyses confirm that Cink4T blocks cells at both G(0)/G(1) and M phases as it should if it were to inhibit both Cdk4 and tubulin polymerization. Our results show, for the very first time, that virtual screening can be used to design novel inhibitors that can potently block two crucial phases of the cell division cycle. (C) 2019 Elsevier Masson SAS. All rights reserved.