含 3-烷氧基亚氨基-4-(甲基)氨基哌啶骨架的喹诺酮/萘啶酮衍生物的合成及体外抗菌活性。

Synthesis and in vitro antibacterial activity of quinolone/naphthyridone derivatives containing 3-alkoxyimino-4-(methyl)aminopiperidine scaffolds.

机构信息

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

出版信息

Bioorg Med Chem Lett. 2013 Mar 15;23(6):1754-9. doi: 10.1016/j.bmcl.2013.01.048. Epub 2013 Jan 24.

DOI:10.1016/j.bmcl.2013.01.048

PMID:23402878

Abstract

We report herein the synthesis of a series of 7-[3-alkoxyimino-4-(methyl)aminopiperidin-1-yl]quinolone/naphthyridone derivatives. In vitro antibacterial activity of these derivatives was evaluated against representative strains, and compared with ciprofloxacin (CPFX), levofloxacin (LVFX) and gemifloxacin (GMFX). The results reveal that all of the target compounds 19a-c and 20 have considerable Gram-positive activity, although they are generally less active than the reference drugs against the Gram-negative strains with some exceptions. Especially, novel compounds 19a2, 19a4 and 19a5 were found to show strong antibacterial activity (MICs: <0.008-0.5μg/mL) against all of the tested 15 Gram-positive strains including MRSA, LVFX- and GMFX-resistant MRSE, and CPFX-, LVFX- and GMFX-resistant MSSA.

摘要

我们在此报告了一系列 7-[3-烷氧基亚氨基-4-(甲基)氨基哌啶-1-基]喹诺酮/萘啶酮衍生物的合成。对这些衍生物进行了针对代表性菌株的体外抗菌活性评估，并与环丙沙星（CPFX）、左氧氟沙星（LVFX）和加替沙星（GMFX）进行了比较。结果表明，所有目标化合物 19a-c 和 20 都具有相当强的革兰氏阳性活性，尽管它们通常对革兰氏阴性菌株的活性不如参考药物，但也有一些例外。特别是，新型化合物 19a2、19a4 和 19a5 被发现对所有测试的 15 种革兰氏阳性菌株（包括 MRSA、LVFX 和 GMFX 耐药性 MRSE 以及 CPFX、LVFX 和 GMFX 耐药性 MSSA）具有很强的抗菌活性（MICs：<0.008-0.5μg/mL）。