2-(4-formylphenoxy)-N-(naphthalen-2-yl)acetamide | 17172-55-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(4-formylphenoxy)-N-(naphthalen-2-yl)acetamide
• 英文别名: 2-(4-Formylphenoxy)-N-2-naphthalenylacetamide；2-(4-formylphenoxy)-N-naphthalen-2-ylacetamide
• CAS: 17172-55-3
• 化学式: C₁₉H₁₅NO₃
• 分子量: 305.333
• InChiKey: NPRNTOATFRLLNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 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 、 2-(4-formylphenoxy)-N-(naphthalen-2-yl)acetamide 以 乙醇 、 水 为溶剂， 以96.3%的产率得到N-(naphthalen-2-yl)-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：

  2-萘胺 在 potassium carbonate 、 potassium iodide 作用下， 以 溶剂黄146 、 丙酮 为溶剂， 生成 2-(4-formylphenoxy)-N-(naphthalen-2-yl)acetamide
  参考文献：
  名称：

  Cink4T, a quinazolinone-based dual inhibitor of Cdk4 and tubulin polymerization, identified via ligand-based virtual screening, for efficient anticancer therapy

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2019.01.011

文献信息

• 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.
• CYP enzymes, expressed within live human suspension cells, are superior to widely-used microsomal enzymes in identifying potent CYP1A1/CYP1B1 inhibitors: Identification of quinazolinones as CYP1A1/CYP1B1 inhibitors that efficiently reverse B[a]P toxicity and cisplatin resistance
  作者：Vinay R. Sonawane、Mohd Usman Mohd Siddique、Linda Gatchie、Ibidapo S. Williams、Sandip B. Bharate、Venkatesan Jayaprakash、Barij N. Sinha、Bhabatosh Chaudhuri

  DOI：10.1016/j.ejps.2019.02.016

  日期：2019.4

  Microsomal cytochrome P450 (CYP) enzymes, isolated from recombinant bacterial/insect/yeast cells, are extensively used for drug metabolism studies. However, they may not always portray how a developmental drug would behave in human cells with intact intracellular transport mechanisms. This study emphasizes the usefulness of human HEK293 kidney cells, grown in 'suspension' for expression of CYPs, in finding potent CYP1A1/CYP1B1 inhibitors, as possible anticancer agents. With live cell-based assays, quinazolinones 9i/9b were found to be selective CYP1A1/CYP1B1 inhibitors with IC50 values of 30/21 nM, and > 150-fold selectivity over CYP2/3 enzymes, whereas they were far less active using commercially-available CYP1A1/CYP1B1 microsomal enzymes (IC50, > 10/1.3-1.7 mu M). Compound 9i prevented CYP1A1-mediated benzo [a]pyrene-toxicity in normal fibroblasts whereas 9b completely reversed cisplatin resistance in PC-3/prostate, COR-L23/1ung, MIAPaCa-2/pancreatic and LS174T/colon cancer cells, underlining the human-cell-assays' potential. Our results indicate that the most potent CYP1A1/CYP1B1 inhibitors would not have been identified if one had relied merely on microsomal enzymes.
• Synthesis and biological activity of novel barbituric and thiobarbituric acid derivatives against non-alcoholic fatty liver disease
  作者：Liang Ma、Shilin Li、Hao Zheng、Jinying Chen、Lin Lin、Xia Ye、Zhizhi Chen、Qinyuan Xu、Tao Chen、Jincheng Yang、Neng Qiu、Guangcheng Wang、Aihua Peng、Yi Ding、Yuquan Wei、Lijuan Chen

  DOI：10.1016/j.ejmech.2011.02.033

  日期：2011.6

  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.
• 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.