2-(4-fluorobenzyl)-5-aminobenzoxazole | 959958-63-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: 2-(4-fluorobenzyl)-5-aminobenzoxazole
• 英文别名: 2-[(4-fluorophenyl)methyl]-1,3-benzoxazol-5-amine
• CAS: 959958-63-5
• 化学式: C₁₄H₁₁FN₂O
• mdl: MFCD09940518
• 分子量: 242.253
• InChiKey: MALNVLXZEIOIOY-UHFFFAOYSA-N

物化性质

• 沸点：
  421.3±30.0 °C(Predicted)
• 密度：
  1.306±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  52
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-fluorobenzyl)-5-aminobenzoxazole 在 碳酸氢钠 、 三乙胺 作用下， 以 乙醚 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 2-(p-fluorobenzyl)-5-[3-[4-(p-chlorophenyl)piperazin-1-yl]propionamido]benzoxazole
  参考文献：
  名称：

  Arisoy, Mustafa; Temiz-Arpaci, Ozlem; Kaynak-Onurdag, Fatma, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2016, vol. 55B, # 2, p. 240 - 247

  摘要：

  DOI：
• 作为产物：
  描述：

  2-(p-fluorobenzyl)-5-nitrobenzoxazole 在 nickel(II) chloride hexahydrate 、 锌 作用下， 以 甲醇 为溶剂， 生成 2-(4-fluorobenzyl)-5-aminobenzoxazole
  参考文献：
  名称：

  Synthesis, biological evaluation and 2D-QSAR analysis of benzoxazoles as antimicrobial agents

  摘要：

  A new series of 5(or 6)-nitro/amino-2-(substituted phenyl/benzyl)benzoxazole derivatives (1a-1m, 2a-21) were synthesized and evaluated for antibacterial and antifungal activities against Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and their drug-resistant isolate. Microbiological results indicated that the synthesized compounds possessed a broad spectrum of activity against the tested microorganisms at MIC values between >400 and 12.5 mu g/ml. The results against B. subtilis, P. aeruginosa, drug-resistant B. subtilis, drug-resistant E. coli, and C. albicans isolate for these kinds of structures are quite encouraging. The 2D-QSAR analysis of a set of newly and previously synthesized benzoxazoles tested for growth inhibitory activity against B. subtilis ATCC 6633 was performed by using the multivariable regression analysis. The activity contributions for substituent effects of these compounds were determined from the correlation equation for predictions of the lead optimization. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.04.001

文献信息

• Synthesis, antimicrobial activity, pharmacophore analysis of some new 2-(substitutedphenyl/benzyl)-5-[(2-benzofuryl)carboxamido]benzoxazoles
  作者：Sabiha Alper-Hayta、Mustafa Arisoy、Özlem Temiz-Arpaci、Ilkay Yildiz、Esin Aki、Semiha Özkan、Fatma Kaynak

  DOI：10.1016/j.ejmech.2007.12.019

  日期：2008.11

  The synthesis and antimicrobial activity of a new series of 2-(substitutedphenyl/benzyl)-5-[(2-benzofuryl)carboxamido]benzoxazole derivatives 3-12 were described. The in vitro antimicrobial activity of the compounds was determined against some Gram-positive, Gram-negative bacteria and fungi and their drug-resistant isolates in comparison with standard drugs. Antimicrobial results indicated that the

  描述了一系列新的2-（取代的苯基/苄基）-5-[（2-苯并呋喃基）羧酰胺基]苯并恶唑衍生物3-12的合成和抗菌活性。与标准药物相比，确定了该化合物对某些革兰氏阳性，革兰氏阴性细菌和真菌及其耐药分离株的体外抗菌活性。抗菌结果表明，合成的化合物具有广谱的活性，MIC值为500-15.625 microg / ml。在该系列中，对克鲁斯假丝酵母和白色念珠菌分离物最有活性的化合物是8，MIC值为31.25 microg / ml。但是，它的稀释度比氟康唑的稀释度低。某些筛选的化合物表现出显着的活性，在铜绿假单胞菌中具有与利福平相同的活性，MIC值为31.25 microg / ml。
• Synthesis, molecular docking and antimicrobial evaluation of novel benzoxazole derivatives
  作者：Tugba Ertan-Bolelli、İlkay Yildiz、Selda Ozgen-Ozgacar

  DOI：10.1007/s00044-015-1499-1

  日期：2016.4

  research, previously and newly synthesized 5-amino-2-(4-substitutedphenyl/benzyl)benzoxazoles (3a–3l) and 2-substituted-5-(4-nitro/aminophenylsulfonamido)benzoxazoles (5a–5l, 6a–6l) were evaluated for their antimicrobial activities against Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29212 and Mycobacterium tuberculosis H37RV

  在这项研究中，以前和新合成的5-氨基-2-（4-取代的苯基/苄基）苯并恶唑（3a - 3l）和2-取代的5-（4-硝基/氨基苯基磺酰胺基）苯并恶唑（5a - 5l，6a - 6l）它们对抗菌活性进行了评价铜绿假单胞菌ATCC 27853，金黄色葡萄球菌ATCC 29213，大肠杆菌ATCC 25922，粪肠球菌ATCC 29212和结核分枝杆菌H37RV ATCC 27294及其耐药株白色念珠菌ATCC 10231和克柔念珠菌ATCC 6258.通过IR，1 H NMR，13 C NMR，LC-MS和元素分析对新合成化合物的化学结构进行了表征。微生物学结果表明，该化合物在256至8 µg / mL的最低抑菌浓度（MIC）值下具有广泛的针对被测微生物的活性。化合物3a，3c和3f表现出显着的抗分枝杆菌活性，对两种M的MIC值为8 µg / mL 。结核病及其耐药分离株。InhA，来自M的烯酰
• 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。
• Biological activity and ADME/Tox prediction of some 2-substituted benzoxazole derivatives
  作者：Fatma Zilifdar Foto、Egemen Foto、Tugba Ertan-Bolelli、Ilkay Yildiz

  DOI：10.1016/j.bioorg.2022.105756

  日期：2022.6

  some in vitro biological activities of a series of (5 or 6)-amino-2- (substituted phenyl and benzyl) benzoxazole derivatives. For this purpose, we tested cytotoxic and genotoxic activities of them on cancer cell lines and their topoisomerase inhibitory activities. We also tested their cytotoxic and genotoxic activities on non-cancerous cells (L929) and their mutagenic activities by Ames test to evaluate

  在这项研究中，我们主要关注一系列（5或6）-氨基-2-（取代的苯基和苄基）苯并恶唑衍生物的一些体外生物活性。为此，我们测试了它们对癌细胞系的细胞毒性和基因毒性活性及其拓扑异构酶抑制活性。我们还通过 Ames 测试测试了它们对非癌细胞 (L929) 的细胞毒性和基因毒性活性以及它们的诱变活性，以评估它们对健康细胞的影响。在所有测试的癌细胞系中，仅发现TD5具有细胞毒性，并且对健康细胞没有表现出细胞毒性或基因毒性活性，而TD1、TD2、TD3和TD7仅对 HeLa 细胞具有更强的细胞毒性。仅TD4被发现是诱变衍生物。没有一种化合物具有任何拓扑异构酶抑制活性，但是它们中的一些引起了对拓扑异构酶II活性的抑制。此外，我们使用计算机模型来预测它们的类药物特性，以评估它们对 QikProp 特性预测的生物利用度。所有计算的属性都在允许的范围内。根据生物活性研究的数据，可以得出结论，苯并恶唑环2位的亚甲
• A study on the genotoxic activities of some new benzoxazoles
  作者：Emine Oksuzoglu、Ozlem Temiz-Arpaci、Betul Tekiner-Gulbas、Hatice Eroglu、Gulseren Sen、Sabiha Alper、Ilkay Yildiz、Nuran Diril、Esin Aki-Sener、Ismail Yalcin

  DOI：10.1007/s00044-007-9005-z

  日期：2008.1

  The Bacillus subtilis rec assay has been specially developed to detect DNA-damaging potential in chemicals, with the rationale based on the relative difference of survival of a DNA repair combination proficient strains and its deficient strain, which is interpreted as genotoxicity. The genotoxic activities of newly (1-6) and previously (7-18) synthesized various benzoxazoles and benzimidazoles were analyzed via the B. subtilis rec assay. Newly obtained benzoxazole and benzimidazole derivatives (1-6) were synthesized in the presence of polyphosphoric acid (PPA) and 6 N HCl, respectively to detect their DNA-damaging activities. Among the tested compounds, 6-methyl-2-(o-chlorophenyl)benzoxazole (9), 5-amino-2-(p-methylbenzyl)benzoxazole (4), 5-(p-fluorobenzamido)-2-phenylbenzoxazole (13), and 2-(p-methylaminophenyl)benzoxazole (18) showed genotoxic activities having ReC50 values of 1.85, 1.74, 1.60, and 1.50 or S-probit values of 0.534, 0.482, 0.460, and 0.357, respectively. On the other hand, 2-(p-bromobenzyl)5-methylbenzimidazole (6) and 2-benzyl-5-(p-fluorophenylacetamido)-benzoxazole (15) were exhibited a reverse effect that displayed a bacterial growth in the rec strains while there was no any bacterial growth in rec(+) strains at the same concentration.