189498-33-7Relevant academic research and scientific papers
Synthesis and antimicrobial activity of 4H-4-oxoquinolizine derivatives: Consequences of structural modification at the C-8 position
Ma, Zhenkun,Chu, Daniel T. W.,Cooper, Curt S.,Li, Qun,Fung, Anthony K. L.,Wang, Sanyi,Shen, Linus L.,Flamm, Robert K.,Nilius, Angela M.,Alder, Jeffery D.,Meulbroek, Jonathan A.,Or, Yat Sun
, p. 4202 - 4213 (2007/10/03)
The antibacterial 4H-4-oxoquinolizines were introduced recently to overcome bacterial resistance to fluoroquinolones. They exhibit potent antibacterial activity against Gram-positive, Gram-negative, and anaerobic organisms and are highly active against some quinolone-resistant bacteria including quinolone-resistant MRSA. Preliminary studies indicated that oxoquinolizines possess distinct activity and toxicity profiles as compared with their parent quinolones. In order to develop a potent antibacterial agent with the desired spectrum of activity, good tolerability, and balanced pharmacokinetic profile, we synthesized and evaluated a series of oxoquinolizines with various substituents at the C-8 position. Most compounds tested in this study demonstrated better activity against Gram-positive bacteria than ciprofloxacin and exhibited good susceptibility against ciprofloxacin- and methicillin-resistant S. aureus. While maintaining potent in vitro activity, several compounds showed improved in vivo efficacy over ABT-719 as indicated by the mouse protection test. As an example, the oral ED50 values for the cis-3-amino-4-methylpiperidine analogue 3ss against S. aureus NCTC 10649M, S. pneumoniae ATCC 6303, and E. coli JUHL were 0.8, 2.0, and 1.4 mg/kg, compared to 3.0, 10.0, and 8.3 mg/kg for ABT-719. The current study revealed that the steric and electronic environment conformation, and absolute stereochemistry of the C-8 group are very important to the antibacterial profiles. Structural modifications of the C-8 group provide a useful means to improve the antibacterial activities, physicochemical properties, and pharmacokinetic profiles. Manipulation of the C-8 group also allows us to generate analogues with the desired spectrum of activity, such as analogues that are selective against respiratory pathogens.
Asymmetric dipolar cycloaddition reactions: A practical, convergent synthesis of chiral pyrrolidines
Ma, Zhenkun,Wang, Sanyi,Cooper, Curt S.,Fung, Anthony K. L.,Lynch, John K.,Plagge, Frederick,Chu, Daniel T. W.
, p. 883 - 887 (2007/10/03)
Chiral trans-3,4-disubstituted pyrrolidines were obtained from the 1,3-dipolar cycloaddition of chiral α,β-unsaturated N-acyloxazolidinones and azomethine ylide.
