Document Report Card

ID: ALA1125733

Journal: J Med Chem

Title: Fluoronaphthyridines and -quinolones as antibacterial agents. 3. Synthesis and structure-activity relationships of new 1-(1,1-dimethyl-2-fluoroethyl), 1-[1-methyl-1-(fluoromethyl)-2-fluoroethyl], and 1-[1,1-(difluoromethyl)-2-fluoroethyl] substituted derivatives.

Authors: Remuzon P, Bouzard D, Cesare PD, Essiz M, Jacquet JP, Kiechel JR, Ledoussal B, Kessler RE, Fung-Tomc J.

Abstract: A series of novel N-1-(mono-,-(di- and -(trifluoro-tert-butyl)quinolones and -naphthyridines has been prepared. Structure-activity relationship (SAR) studies indicated that the in vitro antibacterial potency was the following order: 1-(1,1-dimethyl-2-fluoroethyl) greater than 1-[1-methyl-1-(fluoromethyl)-2-fluoroethyl] greater than 1-[1,1-(difluoromethyl)-2-fluoroethyl] substituents. In the quinolone series the monofluoro-tert-butyl derivatives were found to possess better in vitro antibacterial activity than the nonfluorinated-tert-butyl equivalents. In vivo PD50 values of the 1-fluoro-tert-butyl-substituted derivatives reflect pharmacokinetic behavior and incomplete oral absorption.

CiteXplore: 1992128

DOI: 10.1021/jm00105a006