Synthesis and structure-activity relationship studies of novel [6,6,5] tricyclic oxazolidinone derivatives as potential antibacterial agents.
Synthesis and structure-activity relationship studies of novel [6,6,5] tricyclic oxazolidinone derivatives as potential antibacterial agents.
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DOI：
10.1016/j.bmcl.2015.03.053
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发表时间：
2015-05
影响因子：
2.7
通讯作者：
Tao Xue;Shi Ding;Bin Guo;Wenjing Chu;H. Wang;Yushe Yang
中科院分区：
文献类型：
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作者：
Tao Xue;Shi Ding;Bin Guo;Wenjing Chu;H. Wang;Yushe Yang
在我们的前一封信中，我们报告了一种新的苯并恶嗪基恶唑烷酮抗菌候选物的发现2。为了鉴定潜在的备用化合物，对B/C环和C3侧链进行了广泛的修饰。合成了一系列新型[6，6，5]三环类似物，并测试了它们对一组敏感和耐药革兰氏阳性病原菌的体外抗菌活性。其中，以乙酰胺或硫代酰胺为C3侧链的苯并噻嗪基恶唑烷酮类化合物表现出中等至良好的抗菌活性，如化合物54、58、59和63。进一步评价了化合物54和58的体外肝微粒体稳定性，结果表明化合物54和58在大鼠和人肝微粒体中均具有代谢稳定性。此外，从这项调查中获得的见解应该为新的恶唑烷酮抗生素的进一步研究提供方向。
In our previous Letter, we reported the discovery of a novel benzoxazinyl-oxazolidinone antibacterial candidate2. In order to identify a potential backup compound, extensive modifications on the B/C ring and C3 side chain were undertaken. A series of novel [6,6,5] tricyclic analogues were synthesized and their in vitro antibacterial activities were tested against a panel of susceptible and resistant Gram-positive pathogens. Among of them, benzothiazinyl-oxazolidinones with acetamide or thioamide as C3 side chains exhibited moderate to good antibacterial activity, such as compounds54,58,59and63. In vitro liver microsomal stability was further evaluated and the results manifested that compounds54and58were both metabolically stable in rat and human liver microsomes. Additionally, insights gained from this investigation should provide directions for the further research of new oxazolidinone antibiotics.