A series of 9-O-(3-aryl-2-propargyl)oxime ketolides 8 was synthesized and evaluated for in vitro antibacterial activity. Among 8, 8b-8d, and 8h-8l displayed dramatically improved potency against inducibly MLS(B)-resistant and efflux-resistant pathogens as compared to clarithromycin and azithromycin. Especially, 8i (Ar=4-isoquinolyl) possessed an MIC of 0.064 μg/mL against constitutively MLS(B)-resistant Streptococcus pneumoniae, and MICs of 0.032-0.064 μg/mL against methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus hominis. The analog 10 with a propyl linker was less effective than both the corresponding 8 and 9 containing propynyl and propenyl linkers. A docking study was performed to gain insight into the binding mode of series 8 and 9 and to rationalize the disparity found in the SAR of 8 and 9.

译文

:合成了一系列9-O-(3-芳基-2-炔丙基)肟酮醇酯8,并评价了其体外抗菌活性。与克拉霉素和阿奇霉素相比,在8、8b-8d和8h-8l中显示出对诱导性MLS(B)耐药和外流耐药病原体的效力显着提高。特别是8i(Ar = 4-异喹啉基)对组成型MLS(B)耐药的肺炎链球菌的MIC为0.064μg/ mL,对耐甲氧西林的金黄色葡萄球菌和耐甲氧西林的金黄色葡萄球菌的MIC为0.032-0.064μg/ mL 。具有丙基接头的类似物10比相应的含有丙炔基和丙烯基接头的8和9的效力差。进行了对接研究,以了解8和9系列的结合模式并合理化8和9 SAR中的差异。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录