Hu Wenhao, Bürli Roland W, Kaizerman Jacob A, Johnson Kirk W, Gross Matthew I, Iwamoto Mari, Jones Peter, Lofland Denene, Difuntorum Stacey, Chen Hsiu, Bozdogan Bülent, Appelbaum Peter C, Moser Heinz E
Genesoft Pharmaceuticals, Inc., 7300 Shoreline Court, South San Francisco, California 94080, USA.
J Med Chem. 2004 Aug 26;47(18):4352-5. doi: 10.1021/jm049712g.
Potent in vivo activity against methicillin-resistant Staphylococcus aureus (MRSA) has been difficult to achieve with previously reported DNA binding antibacterials. Herein, we describe an efficient access to a focused library of new analogues yielding compounds with improved activity in a mouse peritonitis model. The most potent molecules (14 and 19) exhibit efficacy against MRSA at ED50 values of approximately 1 and approximately 5 mg/kg, respectively, and display excellent in vitro activity against vancomycin-resistant S. aureus.
对于先前报道的DNA结合抗菌药物而言，在体内对耐甲氧西林金黄色葡萄球菌（MRSA）产生强效活性一直难以实现。在此，我们描述了一种高效构建聚焦新类似物文库的方法，该文库产生的化合物在小鼠腹膜炎模型中具有增强的活性。最具活性的分子（14和19）分别在约1mg/kg和约5mg/kg的ED50值下对MRSA表现出疗效，并且对耐万古霉素金黄色葡萄球菌显示出优异的体外活性。
