Synthesis and in vitro antibacterial activity of 7-(3-alkoxyimino-5-amino/methylaminopiperidin-1-yl)fluoroquinolone derivatives

We report herein the design and synthesis of novel 7-(3-alkoxyimino-5-amino/methylaminopiperidin-1-yl)fluoroquinolone derivatives based on the structures of new fluoroquinolones IMB and DZH. The antibacterial activity of these newly synthesized compounds was also evaluated and compared with gemifloxacin, ciprofloxacin, and levofloxacin. Results revealed that all of the target compounds 10–27 have good potency in inhibiting the growth of Staphylococcus aureus including MSSA (MIC: 0.125–8 μg/mL), Staphylococcus epidermidis including MRSE (MIC: 0.25–16 μg/mL), Streptococcus pneumoniae (MIC: 0.125–4 μg/mL), and Escherichia coli (MIC: 0.25–0.5 μg/mL). In particular, some compounds showed useful activity against several fluoroquinolone-resistant strains, and the most active compound 15 was found to be 16–128, 2–32, and 4–8-fold more potent than the three reference drugs against fluoroquinolone-resistant MSSA, MRSA, and MRSE.

Graphical abstractA series of novel 7-(3-alkoxyimino-5-amino/methylaminopiperidin-1-yl)fluoroquinolone derivatives were designed, synthesized and evaluated for their in vitro antibacterial activity compared with gemifloxacin, ciprofloxacin and levofloxacin. All of the target compounds 10–27 have good activity against Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Escherichia coli. In particular, some compounds showed useful activity against several fluoroquinolone-resistant strains, and the most active compound 15 was found to be 16–128, 2–32, and 4–8-fold more potent than the three reference drugs against fluoroquinolone-resistant MSSA, MRSA, and MRSE.Figure optionsDownload full-size imageDownload as PowerPoint slide