Document Report Card

ID: ALA1124180

Journal: J Med Chem

Title: 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.

Authors: Rosen T, Chu DT, Lico IM, Fernandes PB, Shen L, Borodkin S, Pernet AG.

Abstract: 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.

CiteXplore: 3397996

DOI: 10.1021/jm00403a017