ethyl 4-methyl-2-[(4-nitrophenyl)carbonylamino]-1,3-thiazole-5-carboxylate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 4-methyl-2-[(4-nitrophenyl)carbonylamino]-1,3-thiazole-5-carboxylate
• 英文别名: Ethyl 4-methyl-2-(4-nitrobenzamido)-1,3-thiazole-5-carboxylate；ethyl 4-methyl-2-[(4-nitrobenzoyl)amino]-1,3-thiazole-5-carboxylate
• 化学式: C₁₄H₁₃N₃O₅S
• mdl: MFCD01021048
• 分子量: 335.34
• InChiKey: ABSLFYBLTNNUMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  142
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 4-methyl-2-[(4-nitrophenyl)carbonylamino]-1,3-thiazole-5-carboxylate 在 一水合肼 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 20.17h， 生成 N-(5-(4-(((4-fluorophenyl)amino)methyl)-5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)-4-methylthiazol-2-yl)-4-nitrobenzamide
  参考文献：
  名称：

  Synthetic modifications in ethyl 2-amino-4-methylthiazole-5-carboxylate: 3D QSAR analysis and antimicrobial study

  摘要：

  Ethyl 2-amino-4-methylthiazole-5-carboxylate (1) is a very substantial derivative of the thiazole group. This derivative has been modified and has been synthesized using readily available materials. The structures of synthesized derivatives were confirmed by IR, H-1 NMR, C-13 NMR, and mass spectral techniques. The newly prepared compounds (5a-k) were studied for their antimicrobial activities against strains of bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes) and fungi (Candida albicans, Aspergillus niger, and Aspergillus clavatus) using serial dilution method. Structure-activity relationship was carried out by CoMFA and CoMSIA with the help of 3D-QSAR analysis. As per the database alignment, the CoMFA and CoMSIA models were developed. Information based on these models is useful for structure-activity relationships of the reported molecules.[GRAPHICS].

  DOI：

  10.1080/00397911.2019.1587777
• 作为产物：
  描述：

  2-氯乙酰乙酸乙酯 在 吡啶 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 生成 ethyl 4-methyl-2-[(4-nitrophenyl)carbonylamino]-1,3-thiazole-5-carboxylate
  参考文献：
  名称：

  2-苯甲酰胺基-4-甲基噻唑-5-羧酸衍生物作为潜在的黄嘌呤氧化酶抑制剂和自由基清除剂

  摘要：

  新的化学实体非布司他和托吡司他已获得美国食品和药物管理局的批准，为开发除嘌呤以外的不同杂环作为黄嘌呤氧化酶 (XO) 抑制剂开辟了新途径。合成了不同系列的取代 2-苯甲酰胺基-4-甲基噻唑-5-羧酸衍生物 (5a-r)，并通过 IR、1H 和 13C NMR 以及质谱的共同使用表征，用于治疗痛风和高尿酸血症. 合成衍生物的体外研究表明，5b 中对位的氟基团 (IC50 = 0.57 μm) 和 5c 中的氯基团 (IC50 = 0.91 μm) 表明该系列中优异的 XO 抑制活性，以及它们的 DPPH 自由基清除活性。体内血清尿酸抑制研究确定，5b 和 5c 分别显示 62% 和 53% 的尿酸抑制。酶动力学研究表明，5b 是一种混合型抑制剂。各种软件的计算机模拟预测也有助于识别有效的 XO 抑制剂。

  DOI：

  10.1002/ardp.201600313

文献信息

• 2-Benzamido-4-methylthiazole-5-carboxylic Acid Derivatives as Potential Xanthine Oxidase Inhibitors and Free Radical Scavengers
  作者：Md. Rahmat Ali、Suresh Kumar、Obaid Afzal、Nishtha Shalmali、Wazid Ali、Manju Sharma、Sandhya Bawa

  DOI：10.1002/ardp.201600313

  日期：2017.2

  treatment of gout and hyperuricemia. In vitro studies of the synthesized derivatives revealed that the presence of a fluoro group at the para position in 5b (IC50 = 0.57 μm) and a chloro group in 5c (IC50 = 0.91 μm) signifies excellent XO inhibitory activity among the series, along with their DPPH free radial scavenging activity. In vivo serum uric acid inhibition studies established that 5b and 5c

  新的化学实体非布司他和托吡司他已获得美国食品和药物管理局的批准，为开发除嘌呤以外的不同杂环作为黄嘌呤氧化酶 (XO) 抑制剂开辟了新途径。合成了不同系列的取代 2-苯甲酰胺基-4-甲基噻唑-5-羧酸衍生物 (5a-r)，并通过 IR、1H 和 13C NMR 以及质谱的共同使用表征，用于治疗痛风和高尿酸血症. 合成衍生物的体外研究表明，5b 中对位的氟基团 (IC50 = 0.57 μm) 和 5c 中的氯基团 (IC50 = 0.91 μm) 表明该系列中优异的 XO 抑制活性，以及它们的 DPPH 自由基清除活性。体内血清尿酸抑制研究确定，5b 和 5c 分别显示 62% 和 53% 的尿酸抑制。酶动力学研究表明，5b 是一种混合型抑制剂。各种软件的计算机模拟预测也有助于识别有效的 XO 抑制剂。
• Synthetic modifications in ethyl 2-amino-4-methylthiazole-5-carboxylate: 3D QSAR analysis and antimicrobial study
  作者：Nisheeth C. Desai、Nayan B. Bhatt、Surbhi B. Joshi

  DOI：10.1080/00397911.2019.1587777

  日期：2019.4.18

  Ethyl 2-amino-4-methylthiazole-5-carboxylate (1) is a very substantial derivative of the thiazole group. This derivative has been modified and has been synthesized using readily available materials. The structures of synthesized derivatives were confirmed by IR, H-1 NMR, C-13 NMR, and mass spectral techniques. The newly prepared compounds (5a-k) were studied for their antimicrobial activities against strains of bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes) and fungi (Candida albicans, Aspergillus niger, and Aspergillus clavatus) using serial dilution method. Structure-activity relationship was carried out by CoMFA and CoMSIA with the help of 3D-QSAR analysis. As per the database alignment, the CoMFA and CoMSIA models were developed. Information based on these models is useful for structure-activity relationships of the reported molecules.[GRAPHICS].
• Thiazole-5-carboxylic acid derivatives as potent xanthine oxidase inhibitors: design, synthesis, in vitro evaluation, and molecular modeling studies
  作者：Gurinder Kaur、Jatinder V. Singh、Manish K. Gupta、Kavita Bhagat、Harmandeep K. Gulati、Atamjit Singh、Preet Mohinder S. Bedi、Harbinder Singh、Sahil Sharma

  DOI：10.1007/s00044-019-02461-y

  日期：2020.1

  A series of 22 compounds of thiazole-5-carboxylic acid derivatives was rationally designed and synthesized. All the compounds were characterized by using 1H and 13C NMR and tested against xanthine oxidase enzyme by spectrophotometric assay. Majority of the compounds were found active against the enzyme amongst which GK-20 with an IC50 value of 0.45 µM was found to be most potent. Structure-activity

  合理设计合成了22种噻唑-5-羧酸衍生物化合物。所有化合物均使用1 H和13 C NMR进行了表征，并通过分光光度法对黄嘌呤氧化酶进行了测试。发现大多数化合物对酶具有活性，其中IC 50值为0.45 µM的GK-20最有效。从生物学结果获得的构效关系表明，作为环B的二取代化合物比单取代衍生物更有效。帕拉B环上的β-取代对于黄嘌呤氧化酶抑制潜力至关重要。酶动力学研究进一步揭示了它们的混合型抑制行为。此外，通过使用对接研究进一步分析了酶的非布索坦结合位点内最有效的化合物GK-20的结合模式，结果表明该结合剂充分阻断了催化活性位点，阻止了底物结合。