179740-35-3

Upstream product

• 453-71-4 3-nitro-4-fluorobenzoic acid 
• 332370-72-6 N-(tert-butoxycarbonyl)-4-fluoro-3-nitroaniline 
• 361548-95-0 (3-amino-4-fluorophenyl)carbamic acid t-butyl ester 
• 96568-05-7 2,6-dichloro-α-(ethoxymethylene)-5-fluoro-β-oxo-3-pyridinepropanoic acid ethyl ester 
• 96568-04-6 ethyl 3-(2,6-dichloro-5-fluoropyridin-3-yl)-3-oxopropanoate 
• 400-94-2 4-fluoro-3-nitrobenzoyl chloride 
• 456-22-4 4-Fluorobenzoic acid 
• 535170-22-0 ethyl 1-(3-tert-butoxycarbonylamino-4-fluorophenyl)-7-chloro-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate 

Relevant academic research and scientific papers

A novel antibacterial 8-chloroquinolone with a distorted orientation of the N1-(5-amino-2,4-difluorophenyl) group

Fluoroquinolones represent a major class of antibacterial agents with great therapeutic potential. In this study, we designed m-aminophenyl groups as novel N-1 substituents of naphthyridones and quinolones. Among newly synthesized compounds, 7-(3-aminoazetidin-1-yl)-1-(5-amino-2,4-difluorophenyl)-8-chloro-6- fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (4) has extremely potent antibacterial activities against Gram (+) as well as Gram (-) bacteria. This compound is significantly more potent than trovafloxacin against clinical isolates: 30 times against Streptococcus pneumoniae and 128 times against methicillin resistant Staphylococcus aureus. The structure-activity relationship (SAR) study revealed that a limited combination of 1-(5-amino-2,4-difluorophenyl) group, 7-(azetidin-1-yl) group, and 8-Cl atom (or Br atom or Me group) gave potent antibacterial activity. An X-ray crystallographic study of a 7-(3-ethylaminoazetidin-1-yl)-8-chloro derivative demonstrated that the N-1 aromatic group was remarkably distorted out of the core quinolone plane by steric repulsion between the C-8 Cl atom and the N-1 substituent. Furthermore, a molecular modeling study of 4 and its analogues demonstrated that a highly distorted orientation was induced by a steric hindrance of the C-8 substituent, such as Cl, Br, or a methyl group. Thus, their highly strained conformation should be a key factor for the potent antibacterial activity.