Synthesis and In Vitro Antibacterial Activity of 7‐(3‐Alkoxyimino‐4‐methyl‐4‐methylaminopiperidin‐1‐yl)‐fluoroquinolone Derivatives

Abstract

A series of novel 7-(3-alkoxyimino-4-methyl-4-methylaminopiperidin-1-yl)fluoroquinolone derivatives were designed, synthesized, and characterized by 1H-NMR, MS, and HRMS. These fluoroquinolones were evaluated for their in-vitro antibacterial activity against representative Gram-positive and Gram-negative strains. Generally, all of the target compounds have considerable antibacterial activity against the tested forty strains, and exhibit exceptional potency in inhibiting the growth of methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) ATCC33591 (MICs: 0.06 to 2 microg/mL). In particular, compounds 14, 19, 28, and 29 are fourfold more potent than ciprofloxacin against MSSA 08-49. Compounds 23, 26, and 27 are twofold more potent than ciprofloxacin against MRSA ATCC33591 and MSSA ATCC29213. In addition, compound 14 exhibits excellent activity (MIC: 0.06 microg/mL) against Acinetobactes calcoaceticus, which is two- to 16-fold more potent than the reference drugs gemifloxacin, levofloxacin, and ciprofloxacin.

Exploration of Spirocyclic Derivatives of Ciprofloxacin as Antibacterial Agents

“…The synthesis of target fluoroquinolones 3a – aj commenced with commercially available 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ( 7 ) which was esterified to give ester 8 . The latter was converted to boron chelation complex 9 using the published protocols [ 17 , 18 , 19 ]. In the latter, the chlorine in position 7 is particularly activated towards the nucleophilic aromatic substitution.…”

Synthesis and In‐vitro Antibacterial Activity of 7‐(3‐Aminopyrrolo[3,4‐c]pyrazol‐5(2H,4H,6H)‐yl)‐6‐fluoro‐4‐oxo‐1,4‐dihydroquinoline‐3‐carboxylic Acid Derivatives

“…Finally, the target compounds 8a–g and 9a–g were obtained by the coupling reaction of the intermediates 6a,b with various boric chelates containing quinolone and naphthyridone cores 7 , and then hydrolysis of chelating groups according to well‐established literature procedures 17–19. Table 1 shows the novel fluoroquinolone analogs, yields of the final coupling step, and melting points of the purified compounds.…”

4‐Quinolone Derivatives and Their Activities Against Gram‐negative Pathogens

“…Quinolones with oxime‐functionalized azetidines, pyrrolidines, or piperidines have caused great interests since the discovery of the fourth generation FQs GMFX and its derivatives zabofloxacin as well as DW286, which exhibit excellent in vitro and in vivo activities against both Gram‐positive and Gram‐negative organisms including quinolone‐resistant pathogens and improved pharmacokinetic profiles . Some of them were found to have considerable activities against Gram‐negative bacteria, but few of them were superior to GMFX.…”