Zhang Jing, Yang Qingyi, Cross Jason B, Romero Jan Antoinette C, Poutsiaka Katherine M, Epie Felix, Bevan Douglas, Wang Bin, Zhang Yanzhi, Chavan Ajit, Zhang Xin, Moy Terence, Daniel Anu, Nguyen Kien, Chamberlain Brian, Carter Nicole, Shotwell Joseph, Silverman Jared, Metcalf Chester A, Ryan Dominic, Lippa Blaise, Dolle Roland E
Cubist Pharmaceuticals Inc. , Lexington, Massachusetts 02421, United States.
J Med Chem. 2015 Nov 12;58(21):8503-12. doi: 10.1021/acs.jmedchem.5b00961. Epub 2015 Oct 22.
The emergence and spread of multidrug resistant bacteria are widely believed to endanger human health. New drug targets and lead compounds exempt from cross-resistance with existing drugs are urgently needed. We report on the discovery of azaindole ureas as a novel class of bacterial gyrase B inhibitors and detail the story of their evolution from a de novo design hit based on structure-based drug design. These inhibitors show potent minimum inhibitory concentrations against fluoroquinolone resistant MRSA and other Gram-positive bacteria.
人们普遍认为，多重耐药菌的出现和传播危及人类健康。因此，迫切需要新的药物靶点和与现有药物无交叉耐药性的先导化合物。我们报告了氮杂吲哚脲作为一类新型细菌DNA回旋酶B抑制剂的发现，并详细介绍了基于结构药物设计从全新设计命中物演变而来的过程。这些抑制剂对耐氟喹诺酮的耐甲氧西林金黄色葡萄球菌和其他革兰氏阳性菌显示出有效的最低抑菌浓度。
