Document Detail

Asymmetric synthesis and properties of the enantiomers of the antibacterial agent 7-(3-aminopyrrolidin-1-yl)-1-(2,4-difluorophenyl)-1,4-dihydro-6- fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride.
MedLine Citation:
PMID:  3397996     Owner:  NLM     Status:  MEDLINE    
Compound 1 [7-(3-aminopyrrolidin-1-yl)-1-(2,4-difluorophenyl)-1,4-dihydro-6-f luoro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride] is a potent member of the quinolonecarboxylic acid class of antibacterial agents and is currently undergoing clinical evaluation. We have developed efficient asymmetric syntheses of the enantiomers of this agent. The S-(+) enantiomer 1a is 1-2 log2 dilutions more active than the R-(-) enantiomer 1b against aerobic bacteria and 1-2 or more log2 dilutions more active against anaerobic bacteria in vitro. The enantiomer 1a shows significantly better in vivo activity in a Pseudomonas aeruginosa mouse protection model compared to racemic 1. Coupled with the improved solubility profile of 1a relative to racemic material, these features may be of practical significance from a clinical standpoint.
T Rosen; D T Chu; I M Lico; P B Fernandes; L Shen; S Borodkin; A G Pernet
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  31     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  1988 Aug 
Date Detail:
Created Date:  1988-09-02     Completed Date:  1988-09-02     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1586-90     Citation Subset:  IM    
Abbott Laboratories, Illinois 60064.
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MeSH Terms
Anti-Bacterial Agents / chemical synthesis*
Chemical Phenomena
Gram-Negative Bacteria / drug effects
Gram-Positive Bacteria / drug effects
Microbial Sensitivity Tests
Naphthyridines / chemical synthesis*,  pharmacology
Structure-Activity Relationship
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Fluoroquinolones; 0/Naphthyridines; 100490-36-6/tosufloxacin

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