Identification of 4-substituted 1,2,3-triazoles as novel oxazolidinone antibacterial agents with reduced activity against monoamine oxidase A
Identification of 4-substituted 1,2,3-triazoles as novel oxazolidinone antibacterial agents with reduced activity against monoamine oxidase A
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DOI：
10.1021/jm0400810
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发表时间：
2005-01-27
影响因子：
7.3
通讯作者：
Gravestock, MB
中科院分区：
文献类型：
--
作者：
Reck, F;Zhou, F;Gravestock, MB
恶唑烷酮类抗菌剂是一类很有前途的新型抗菌剂。目前，该领域的研究主要集中在提高安全性和抗菌谱方面。许多恶唑烷酮类药物，包括利奈唑胺（以2 Zyvox销售），是单胺氧化酶A （MAO-A）的抑制剂，具有不良的副作用。最近，人们发现1,2,3-三唑可以很好地取代恶唑烷酮类化合物中传统的乙酰胺功能。我们现在公布的发现，1,2.3-三唑，取代基如甲基，小取代甲基，溴，或线性（sp杂化）基团在4位（化合物如5,16,19和21）是很好的抗菌活性降低或没有。在检测限内，抗MAO-A。这些结果对于开发安全性更高的恶唑烷酮类药物尤其有希望。对MAO-A/MAO-B同源物的对接研究可以使MAO-A SAR合理化；模型。
Oxazolidinones represent a new and promising class of antibacterial agents. Current, research in this area is mainly concentrated on improving the safety profile and the antibacterial spectrum. Many oxazolidinones, including linezolid (marketed as 2 Zyvox), are inhibitors of monoamine oxidase A (MAO-A), which presents an undesired side effect. Recently, it was found that the 1,2,3-triazole is a good replacement for the conventional acetamide functionality found in oxazolidinones. We now disclose the finding that 1,2.3-triazoles bearing, a substituent like methyl, small substituted methyl, bromo, or a linear (sp-hybridized) group at the 4 position (compounds such as 5, 16, 19, and 21) are good antibacterials with reduced or no activity.. within the detection limit of the assay, against MAO-A. The results are especially promising for the development of oxazolidinones with an improved safety profile. The MAO-A SAR can be rationalized on the basis of docking studies to a MAO-A/MAO-B homolog; model.