Vinsova Jarmila, Cermakova Katerina, Tomeckova Alexandra, Ceckova Martina, Jampilek Josef, Cermak Pavel, Kunes Jiri, Dolezal Martin, Staud Frantisek
Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, 500 05 Hradec Kralove, Czech Republic.
Bioorg Med Chem. 2006 Sep 1;14(17):5850-65. doi: 10.1016/j.bmc.2006.05.030. Epub 2006 Jun 19.
Various synthetic pathways of the 30 novel 2-substituted 5,7-di-tert-butylbenzoxazoles as new potential antimicrobial drugs are discussed. The 28 intermediates are described as well. The compounds were characterized by 1H and 13C NMR spectra, MS spectra, IR/UV spectra and by means of CHN analysis. The purity of the final compounds was checked by HPLC and their lipophilicity (log K) was also determined by means of RP-HPLC. In the present study, the correlation between RP-HPLC retention parameter log K (the logarithm of capacity factor K) and various calculated log P data is shown. The target compounds were tested for their in vitro antimycobacterial activity. Several compounds showed antituberculotic activity comparable with or higher than the standard isoniazide. In vitro cytotoxicity testing of the most active benzoxazoles and isoniazide as a reference drug was performed using MTT assay and compared with isoniazide as a reference drug. Structure-activity relationships among the chemical structures, the physical properties and the biological activities of the evaluated compounds are discussed in the article.
讨论了30种新型2-取代5,7-二叔丁基苯并恶唑作为新型潜在抗菌药物的各种合成途径。还描述了28种中间体。通过1H和13C NMR光谱、质谱、红外/紫外光谱以及CHN分析对这些化合物进行了表征。通过高效液相色谱法（HPLC）检测最终化合物的纯度，并通过反相高效液相色谱法（RP-HPLC）测定其亲脂性（log K）。在本研究中，展示了反相高效液相色谱保留参数log K（容量因子K的对数）与各种计算得到的log P数据之间的相关性。对目标化合物进行了体外抗分枝杆菌活性测试。几种化合物显示出与标准异烟肼相当或更高的抗结核活性。使用MTT法对活性最高的苯并恶唑和作为参考药物的异烟肼进行了体外细胞毒性测试，并与作为参考药物的异烟肼进行了比较。文章讨论了所评估化合物的化学结构、物理性质和生物活性之间的构效关系。
