Achillion Pharmaceuticals, Inc., 300 George Street, New Haven, Connecticut 06511, United States.
J Med Chem. 2011 May 12;54(9):3418-25. doi: 10.1021/jm2002124. Epub 2011 Apr 13.
We investigated compounds related to the previously reported antistaphyloccocal agent AVE6971 in an effort to attenuate inhibition of hERG potassium channel current that has been noted for this and related antibacterial drug classes. While most modifications of the original thiophene group compromised antibacterial activity, one selenophene analogue displayed (i) improved activity against the primary target enzyme DNA gyrase, (ii) similar activities against a panel of MRSA clinical isolates, and (iii) reduced hERG channel inhibition.
我们研究了与先前报道的抗葡萄球菌药物 AVE6971 相关的化合物，试图减轻此类及相关抗菌药物类别中已注意到的对 hERG 钾通道电流的抑制作用。虽然原始噻吩基团的大多数修饰都降低了抗菌活性，但一个硒吩类似物表现出 (i) 对主要靶酶 DNA 回旋酶的活性提高，(ii) 对一组耐甲氧西林金黄色葡萄球菌临床分离株的活性相似，以及 (iii) 减少 hERG 通道抑制。
