ANTIBACTERIALS - SYNTHESIS AND STRUCTURE ACTIVITY STUDIES OF 3-ARYL-2-OXOOXAZOLIDINES .1. THE B-GROUP
ANTIBACTERIALS - SYNTHESIS AND STRUCTURE ACTIVITY STUDIES OF 3-ARYL-2-OXOOXAZOLIDINES .1. THE B-GROUP
复制标题
DOI：
10.1021/jm00128a003
复制
发表时间：
1989-08-01
影响因子：
7.3
通讯作者：
FORBES, M
中科院分区：
文献类型：
--
作者：
GREGORY, WA;BRITTELLI, DR;FORBES, M
本文报道了一系列恶唑烷酮类抗菌剂(I)中B基团变化的合成和结构/活性研究。采用了两条合成路线：(1)苯胺与缩水甘油的烷基化反应，然后碳酸酯的二烷基杂环化得到I(A=H，B=OH)，用亲电取代芳香族取代法进一步确定了I的芳香环；(2)取代芳基异氰酸酯与环氧化物的环加成反应得到不同取值的A和B。使用SN2方法将具有B=OH或BR的I转化为其他B官能团。对含有A=乙酰基、异丙基、甲硫基、甲亚磺基、甲磺酰基和磺胺基的化合物I和各种不同的B基团对金黄色葡萄球菌和粪肠球菌的抗菌评价得出结论：在每个A系列中，含有B=氨基酰基的化合物，尤其是乙酰氨基化合物，是活性最高的化合物，其MIC值范围为0.5-4微克/毫升。
The synthesis and structure/activity studies of the effect of varying the "B" group in a series of oxazolidinone antibacterials (I) are described. Two synthetic routes were used: (1) alkylation of aniline with glycidol followed by dialkyl carbonate heterocyclization to afford I (A = H, B = OH), whose arene ring was further elaborated by using electrophilic aromatic substitution methodology, (2) cycloaddition of substituted aryl isocyanates with epoxides to give A and B with a variety of values. I with B = OH or Br were converted to other "B" functionalities by using SN2 methodology. Antibacterial evaluation of compounds I with A = acetyl, isopropyl, methylthio, methylsulfinyl, methylsulfonyl, and sulfonamido and a variety of different "B" groups against Staphylococcus aureus and Enterococcus faecalis concluded that the compounds with B = aminoacyl, and particularly acetamido, were the most active of those examined in each A series, possessing MICs in the range of 0.5-4 .mu.g/mL for the most active compounds described.