5-硝基-2-(4-硝基苄基)苯并恶唑 | 104233-74-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 中文名称: 5-硝基-2-(4-硝基苄基)苯并恶唑
• 英文名称: 5-nitro-2-(4-nitrobenzyl)benzoxazole
• 英文别名: 5-Nitro-2-[(4-nitrophenyl)methyl]-1,3-benzoxazole
• CAS: 104233-74-1
• 化学式: C₁₄H₉N₃O₅
• 分子量: 299.243
• InChiKey: FPJHWNBKMLJUQP-UHFFFAOYSA-N

物化性质

• 沸点：
  518.9±35.0 °C(Predicted)
• 密度：
  1.476±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  118
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  对硝基苯乙酸 、 2-氨基-4-硝基苯酚 在 polyphosphoric acid 作用下， 反应 3.0h， 生成 5-硝基-2-(4-硝基苄基)苯并恶唑
  参考文献：
  名称：

  一些苯并恶唑衍生物的合成、抗菌活性和分子模型研究

  摘要：

  背景：随着传染性疾病的增加和抗药性迅速发展，开发新型抗微生物剂的需求显然。 目的：本研究旨在合成苯并噁唑衍生物，进行抗微生物敏感性测试和计算机解析其作用机制。同时，比较本研究结果与我们小组以前的研究结果，为设计具有更好抗微生物活性的新分子铺平道路。另一个目标是药效团分析和体外ADMET分析。 方法：本研究进行了合成、抗微生物敏感性测试、分子对接、药效团分析和ADMET预测。 结果：抗微生物活性研究表明，合成的化合物在高浓度下对标准菌株和临床分离物具有活性。然后，将抗微生物测试结果与我们小组以前测试的类似苯并噁唑化合物进行比较。本研究发现，在噁唑和苯环之间没有亚甲基桥的苯并噁唑衍生物比有亚甲基桥的更活跃。这也得到了本研究进行的分子建模的确认。计算结果表明，抗菌活性可以通过DNA酶抑制实现。药效团分析表明，氢键受体（HBA）、氢键供体（HBD）和疏水性特征将有助于抑制作用。此外，体外ADMET性质调查表明，这些化合物具有理想的药代动力学。 结论：尽管通过抑制DNA酶的抗菌活性是选择性的，但是合成的化合物的活性比标准高得多。因此，在未来的抗微生物研究中，最好专注于没有亚甲基桥的苯并噁唑衍生物。由于这些化合物具有适当的体外ADMET性质，应该对它们进行筛选，以了解其他药理活性。建议通过体外或体内研究来支持分子建模结果。

  DOI：

  10.2174/1570180819666220408133643

文献信息

• Akbay, Ayseguel; Oeren, Ilkay; Temiz-Arpaci, Oezlem, Arzneimittel-Forschung/Drug Research, 2003, vol. 53, # 4, p. 266 - 271
  作者：Akbay, Ayseguel、Oeren, Ilkay、Temiz-Arpaci, Oezlem、Aki-Sener, Esin、Yalcin, Ismail

  DOI：——

  日期：——
• Vibrational spectroscopic (FT-IR, FT-Raman, 1H NMR and UV) investigations and computational study of 5-nitro-2-(4-nitrobenzyl) benzoxazole
  作者：J.B. Bhagyasree、Hema Tresa Varghese、C. Yohannan Panicker、Jadu Samuel、Christian Van Alsenoy、Kayhan Bolelli、Ilkay Yildiz、Esin Aki

  DOI：10.1016/j.saa.2012.09.032

  日期：2013.2

  The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 5-nitro-2-(4-nitrobenzyl) benzoxazole have been investigated experimentally and theoretically using Gaussian09 software package. Potential energy distribution of the normal modes of vibrations was done using GAR2PED program. The energy and oscillator strength calculated by time dependent density functional theory almost compliments with experimental findings. Gauge-including atomic orbital H-1 NMR chemical shifts calculations were carried out by using B3LYP functional with 6-31G(*) basis set. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization have been analyzed using NBO analysis. MEP was performed by the DFT method and the predicted infrared intensities and Raman activities have also been reported. The calculated geometrical parameters are in agreement with that of similar derivatives. (C) 2012 Elsevier B.V. All rights reserved.
• Synthesis, Antimicrobial Activity, and Molecular Modeling Studies of Some Benzoxazole Derivatives
  作者：Muhammed Tilahun Muhammed、Gulcan Kuyucuklu、Fatma Kaynak-Onurdag、Esin Aki-Yalcin

  DOI：10.2174/1570180819666220408133643

  日期：2022.8

  The need to develop novel antimicrobial agents is apparent as infectious diseases are increasing and resistance is rapidly developing against the drugs used in the treatment.

  This study aimed at the synthesis, antimicrobial susceptibility testing, and computational elucidation of the mechanism of action of benzoxazole derivatives. It also aimed to compare the results obtained in this study with the previous studies by our group. This would pave the way for designing novel molecules with better antimicrobial activity. The other goal was pharmacophore analysis and in silico ADMET analysis of them.

  In this study, synthesis, antimicrobial susceptibility testing, molecular docking, pharmacophore analysis, and ADMET prediction were carried out.

  The antimicrobial activity studies demonstrated that the synthesized compounds were active against standard strains and clinical isolates at high concentrations. Then, the antimicrobial testing results were compared to similar benzoxazoles tested by our group previously. Benzoxazole derivatives without a methylene bridge between oxazole and phenyl ring were found to be more active than those with the methylene bridge. This was also confirmed by molecular modeling undertaken in this study. The computational results indicated that the antibacterial activity could be achieved by DNA gyrase inhibition. Pharmacophore analysis showed that hydrogen bond acceptor (HBA), hydrogen bond donor (HBD), and hydrophobicity features would contribute to the inhibition. In addition, in silico ADMET property investigation of the compounds exhibited that they had the desired pharmacokinetics.

  Although antibacterial activity by inhibiting DNA gyrase is selective, the synthesized compounds were active at much higher concentrations than the standards. Therefore, in prospective antimicrobial studies, it is better to focus on benzoxazole derivatives without the methylene bridge. Since the compounds had suitable in silico ADMET properties, screening them against the other pharmacologic activities should be carried out. It is recommended to support the molecular modeling results with in vitro or in vivo studies.

  背景：随着传染性疾病的增加和抗药性迅速发展，开发新型抗微生物剂的需求显然。 目的：本研究旨在合成苯并噁唑衍生物，进行抗微生物敏感性测试和计算机解析其作用机制。同时，比较本研究结果与我们小组以前的研究结果，为设计具有更好抗微生物活性的新分子铺平道路。另一个目标是药效团分析和体外ADMET分析。 方法：本研究进行了合成、抗微生物敏感性测试、分子对接、药效团分析和ADMET预测。 结果：抗微生物活性研究表明，合成的化合物在高浓度下对标准菌株和临床分离物具有活性。然后，将抗微生物测试结果与我们小组以前测试的类似苯并噁唑化合物进行比较。本研究发现，在噁唑和苯环之间没有亚甲基桥的苯并噁唑衍生物比有亚甲基桥的更活跃。这也得到了本研究进行的分子建模的确认。计算结果表明，抗菌活性可以通过DNA酶抑制实现。药效团分析表明，氢键受体（HBA）、氢键供体（HBD）和疏水性特征将有助于抑制作用。此外，体外ADMET性质调查表明，这些化合物具有理想的药代动力学。 结论：尽管通过抑制DNA酶的抗菌活性是选择性的，但是合成的化合物的活性比标准高得多。因此，在未来的抗微生物研究中，最好专注于没有亚甲基桥的苯并噁唑衍生物。由于这些化合物具有适当的体外ADMET性质，应该对它们进行筛选，以了解其他药理活性。建议通过体外或体内研究来支持分子建模结果。