5-(chloromethyl)-3-(4-fluoro-3-methylphenyl)-1,2,4-oxadiazole | 937629-46-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(chloromethyl)-3-(4-fluoro-3-methylphenyl)-1,2,4-oxadiazole
• CAS: 937629-46-4
• 化学式: C₁₀H₈ClFN₂O
• mdl: MFCD09051121
• 分子量: 226.638
• InChiKey: VYBKTWXZKHHWLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  38.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(chloromethyl)-3-(4-fluoro-3-methylphenyl)-1,2,4-oxadiazole 、 对羟基苯丙酸甲酯 在 水 、 caesium carbonate 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 3-(4-((3-(4-fluoro-3-methylphenyl)-1,2,4-oxadiazol-5-yl)methoxy)phenyl)propanoic acid
  参考文献：
  名称：

  Phenoxymethyl 1,3-oxazoles and 1,2,4-oxadiazoles as potent and selective agonists of free fatty acid receptor 1 (GPR40)

  摘要：

  A screening hit that showed a weak (EC50 = 18 mu M), partial agonistic effect on GPR40 was used a prototype for expedited hit expansion effort using a set of advanced building blocks. The latter yielded several 1,3-oxazoles and 1,2,4-oxadiazoles with significantly improved potency (best EC50 = 0.058 mu M). The lead compounds in each chemotype showed a very good ADME profile (aqueous solubility, plasma protein binding, microsomal stability and membrane permeability) and no appreciable inhibition of key cytochromes P450. The compounds reported are significant new starting points for further preclinical development of future diabetic agents with a mechanism of action for which a first-in-class agent is yet to be approved. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.06.018
• 作为产物：
  描述：

  4-氟-3-甲基苯腈 在 盐酸羟胺 、 sodium carbonate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 5-(chloromethyl)-3-(4-fluoro-3-methylphenyl)-1,2,4-oxadiazole
  参考文献：
  名称：

  取代的 1,2,4-恶二唑类似物的设计、微波辅助合成和表征作为有前景的药理学药物

  摘要：

  恶二唑分子支架具有多种药理活性，例如镇咳、麻醉 [1]、驱虫 [2]、抗 HIV [3]、抗过敏 [4]、抗癌 [5]、抗惊厥 [6]、抗炎 [...] 7]、抗菌[8]、抗血小板、抗血栓形成[9]、杀虫[10]、单胺氧化酶抑制[11]、毒蕈碱受体激动剂[12]和选择性H3受体拮抗剂[13]等特性。受到这些观察结果的鼓舞，并继续我们关于合成具有药理特性的新型杂环化合物 [14-17] 和筛选杂环化合物 [18-20] 的多晶型特性的研究工作，我们决定将二苯甲酮部分加入到1,2,4-恶二唑核（Scheme-I）在微波方法的支持下研究产率和总反应时间。

  DOI：

  10.14233/ajchem.2017.20626

文献信息

• <i>In vitro</i> anti-TB properties, <i>in silico</i> target validation, molecular docking and dynamics studies of substituted 1,2,4-oxadiazole analogues against <i>Mycobacterium tuberculosis</i>
  作者：Pran Kishore Deb、Nizar A. Al-Shar’i、Katharigatta N. Venugopala、Melendhran Pillay、Pobitra Borah

  DOI：10.1080/14756366.2021.1900162

  日期：2021.1.1

  (3a–3i) and identify their putative drug target, molecular docking and dynamics studies were employed against a panel of 20 mycobacterial enzymes reported to be essential for mycobacterial growth and survival. These computational studies revealed polyketide synthase (Pks13) enzyme as the putative target. Moreover, in silico ADMET predictions showed satisfactory properties for these compounds, collectively

  抽象的 结核分枝杆菌(MTB) 多重耐药和广泛耐药（MDR 和 XDR）菌株的惊人增加促使科学界寻找新颖、有效和更安全的治疗方法。为此，我们对一系列 3,5-二取代-1,2,4-恶二唑衍生物 ( 3a-3i ) 进行了针对 MTB H37Rv、MDR 和 XDR 菌株的测试。其中，对三氟苯基取代的恶二唑化合物3a对易感H37Rv和MDR-MTB菌株表现出优异的活性，MIC值分别为8和16 µg/ml。 为了了解这些化合物 ( 3a–3i ) 的作用机制并确定其假定的药物靶点，我们针对据报道对分枝杆菌生长和存活至关重要的 20 种分枝杆菌酶进行了分子对接和动力学研究。这些计算研究表明聚酮合酶 (Pks13) 是假定的靶标。此外，计算机ADMET 预测显示了这些化合物总体上令人满意的特性，使它们（特别是化合物3a ）成为值得进一步优化的有前景的先导化合物。
• Design, synthesis, characterization, and antibacterial activity of {5-chloro-2-[(3-substitutedphenyl-1,2,4-oxadiazol-5-yl)-methoxy]-phenyl}-(phenyl)-methanones
  作者：Neithnadka Premsai Rai、Venugopala Katharigatta Narayanaswamy、Thavendran Govender、B.K. Manuprasad、Sheena Shashikanth、Pirama Nayagam Arunachalam

  DOI：10.1016/j.ejmech.2010.02.021

  日期：2010.6

  In the present investigation, a series of novel 5-chloro-2-[(3-(substitutedphenyl)-1,2,4-oxadiazol-5-yl)-methoxy]-phenyl}-(phenyl)-methanones (3a-i) have been synthesized from 5-(chloromethyl)-3-sub-stitutedphenyl-1,2,4-oxadiazole (2a-i). The newly synthesized compounds were characterized by IR. NMR (H-1 and C-13), mass spectral and elemental analysis. The title compounds were investigated for in-vitro qualitative (zone of inhibition) and quantitative (MIC) antibacterial activity by agar cup plate and microtitration methods, respectively. The minimum inhibitory concentration and structure activity relationships (SARs) were evaluated. Amongst the synthesized compounds in this series, 5-chloro-2-[(3-(2,5-difluoro-4-methyl-phenyl)-1,2,4-oxadiazol-5-yl)-methoxy]-phenyl}-(phenyl)-methanone (3d) was found to exhibit significant activity with MICs of 21.5, 224, 298 and 306 mu g/mL against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae, respectively.