2-(4-甲酰基-2-甲氧基苯氧基)-N-(4-甲氧基苯基)乙酰胺 | 32725-79-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(4-甲酰基-2-甲氧基苯氧基)-N-(4-甲氧基苯基)乙酰胺
• 英文名称: 2-(4-formyl-2-methoxyphenoxy)-N-(4-methoxyphenyl)acetamide
• CAS: 32725-79-4
• 化学式: C₁₇H₁₇NO₅
• mdl: MFCD01542150
• 分子量: 315.326
• InChiKey: NPRXEMVBOBVOCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.176
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  2-(4-甲酰基-2-甲氧基苯氧基)-N-(4-甲氧基苯基)乙酰胺 、 2-氨基苯甲酰胺 在 碘 、 sodium acetate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以77.91%的产率得到2-[2-methoxy-4-(4-oxo-3,4-dihydroquinazolin-2-yl)phenoxy]-N-(4-methoxyphenyl) acetamide
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.ejps.2019.02.016
• 作为产物：
  描述：

  甲氧苯胺 在 potassium carbonate 、 potassium iodide 作用下， 以 丙酮 为溶剂， 反应 4.5h， 生成 2-(4-甲酰基-2-甲氧基苯氧基)-N-(4-甲氧基苯基)乙酰胺
  参考文献：
  名称：

  苯氧基-双香豆素-N-苯乙酰胺杂化物的设计、合成和α-葡萄糖苷酶抑制活性

  摘要：

  基于分子杂交方法设计了13 种新的苯氧基-双香豆素-N-苯乙酰胺衍生物 ( 7a - m ) 作为新的 α-葡萄糖苷酶抑制剂。这些化合物以高产率合成，并在体外评估了它们对酵母α-葡萄糖苷酶的抑制活性。所得结果表明，与作为阳性对照的阿卡波糖相比，大部分合成的化合物显示出相当大的α-葡萄糖苷酶抑制活性。代表性地，2-(4-(双(4-羟基-2-氧代-2H-色烯-3-基)甲基)苯氧基) -N- (4-溴苯基)乙酰胺( 7f )，IC 50 = 41.73 ± 0.38 µM 对抗 α-葡萄糖苷酶，比阿卡波糖强约 18 倍（IC 50  = 750.0 ± 10.0 µM）。该化合物是一种竞争性α-葡萄糖苷酶抑制剂。这些化合物的分子建模和动态模拟通过体外实验证实了所获得的结果。化合物7f的药物相似性/ADME/毒性的预测以及与标准药物阿卡波糖的比较表明，新化合物7f在毒性方面可能优于标准药物。

  DOI：

  10.1002/ardp.202100179

文献信息

• Synthesis and anticancer activity evaluation of 4-thiazolidinones containing benzothiazole moiety
  作者：Dmytro Havrylyuk、Ludmyla Mosula、Borys Zimenkovsky、Olexandr Vasylenko、Andrzej Gzella、Roman Lesyk

  DOI：10.1016/j.ejmech.2010.08.008

  日期：2010.11

  alternatively by a counter synthesis method based on the reaction of 2-chloro-N-(6-methylbenzothiazol-2-yl)-acetamide and ammonium thiocyanate. The structures of compounds have been determined by 1H, 13C NMR, IR and X-ray analysis. In vitro anticancer activity of the synthesized compounds was tested by the National Cancer Institute and two (6, 16) of them has revealed the anticancer activity on leukemia, melanoma

  已经进行了几种具有苯并噻唑部分的新颖的4-噻唑烷酮的抗肿瘤筛选。（苯并噻唑-2-基）肼与三硫代羰基二乙醇酸或6-甲基-2-氨基苯并噻唑与2-乙氧基甲硫基-2-噻唑啉-4-酮的反应产生了起始的3-（1）或2-取代的（11）4这已经在Knoevenagel缩合随后被用于获取一系列5-亚芳基衍生物的-thiazolidinones 2-10，12-16。或者，根据2-氯-N-（6-甲基苯并噻唑-2-基）-乙酰胺与硫氰酸铵的反应，通过反合成方法得到化合物11。化合物的结构由1 H确定，13 C NMR，IR和X射线分析。体外合成的化合物的抗癌活性是由美国国家癌症研究所和两个（测试6，16）的他们已经揭示于白血病，黑色素瘤，肺癌，结肠癌，中枢神经系统癌，卵巢癌，肾癌，前列腺癌和乳腺癌细胞系中的抗癌活性。在测试的化合物中，2- 2- [3-（苯并噻唑-2-基氨基）-4-氧代-2-硫代噻唑烷啶-5-亚甲基甲基]
• Design, synthesis, α‐glucosidase inhibition, pharmacokinetic, and cytotoxic studies of new indole‐carbohydrazide‐phenoxy‐<i>N</i>‐phenylacetamide derivatives
  作者：Haleh Hamedifar、Maryam Mohammadi‐Khanaposhtani、Maedeh Sherafati、Milad Noori、Ali Moazam、Samanesadat Hosseini、Bagher Larijani、Mir H. Hajimiri、Mohammad Mahdavi、Mehmet K. Erdogan、Ramazan Gundogdu、Mahinur Kirici、Parham Taslimi、İlhami Gülçin

  DOI：10.1002/ardp.202200571

  日期：2023.6

  Among them, 2-mehoxy-phenoxy derivatives 7l and 7h with 4-nitro and 4-chloro substituents on the phenyl ring of the N-phenylacetamide moiety, respectively, displayed the most inhibition effects. The inhibitory mechanism of these compounds was investigated by molecular docking studies. The in vitro cytotoxicity assay showed that only one compound, 2-methoxy-phenoxy derivative 7k with a 4-bromo substituent

  设计、合成了一系列新的吲哚-碳酰肼-苯氧基-N-苯基乙酰胺衍生物7a-l，并筛选了它们的 α-葡萄糖苷酶抑制能力和细胞毒性作用。在 α-葡萄糖苷酶抑制试验中获得的结果表明，与标准药物阿卡波糖 ( K i  = 42.38 ) 相比，大多数合成衍生物显示出良好至中度的抑制能力（ K i值范围为 14.65 ± 2.54 至 37.466 ± 6.46 μM） ± 5.73 微米）。其中， N的苯环上有4-硝基和4-氯取代基的2-甲氧基-苯氧基衍生物7l和7h-苯基乙酰胺部分分别显示出最大的抑制作用。通过分子对接研究研究了这些化合物的抑制机制。体外细胞毒性测定表明，只有一种化合物，即在N-苯基乙酰胺部分的苯环上具有 4-溴取代基的2-甲氧基-苯氧基衍生物7k，对人非小细胞肺癌细胞系表现出中等的细胞毒性A549 和其余化合物几乎没有细胞毒性。还对化合物7k进行了进一步的细胞毒性评估。计算机模拟药
• Discovery of novel glitazones incorporated with phenylalanine and tyrosine: Synthesis, antidiabetic activity and structure–activity relationships
  作者：B.R. Prashantha Kumar、Nasir R. Baig、Sai Sudhir、Koyal Kar、M. Kiranmai、M. Pankaj、Nanjan M. Joghee

  DOI：10.1016/j.bioorg.2012.08.002

  日期：2012.12

  We report a series of new glitazones incorporated with phenylalanine and tyrosine. All the compounds were tested for their in vitro glucose uptake activity using rat-hemidiaphragm, both in presence and absence of insulin. Six of the most active compounds from the in vitro screening were taken forward for their in vivo triglyceride and glucose lowering activity against dexamethazone induced hyperlipidemia and insulin resistance in Wistar rats. The liver samples of rats that received the most active compounds, 23 and 24, in the in vivo studies, were subjected to histopathological examination to assess their short term hepatotoxicity. The investigations on the in vitro glucose uptake, in vivo triglyceride and glucose lowering activity are described here along with the quantitative structure-activity relationships. (C) 2012 Elsevier Inc. All rights reserved.
• Novel glitazones: Design, synthesis, glucose uptake and structure–activity relationships
  作者：B.R. Prashantha Kumar、M.J. Nanjan

  DOI：10.1016/j.bmcl.2010.01.125

  日期：2010.3

  Glitazones are known to exhibit antihyperglycemic activity by decreasing peripheral insulin resistance. In the present study, we have designed some novel glitazones based on the structure-activity relationships as possible PPAR-gamma agonists. The manually designed glitazones were synthesized by using the appropriate synthetic schemes and screened for their in vitro antihyperglycemic activity by estimating glucose uptake by rat hemi-diaphragm, both in the absence and in the presence of external insulin. Some of the glitazones exhibited good antihyperglycemic activity in presence of insulin. Illustration about their design, synthesis, evaluation, and structure-activity relationships is described. (C) 2010 Elsevier Ltd. 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.