Fluoronaphthyridines and quinolones as antibacterial agents. 2. Synthesis and structure-activity relationships of new 1-tert-butyl 7-substituted derivatives

Abstract

A number of 7-substituted-1-tert-butyl-6-fluoroquinolone-3-carboxylic acids and 7-substituted-1-tert-butyl-6-fluoro-1,8-naphthyridine-3-carboxylic acids have been prepared and tested for antibacterial activities. Among those the 7-aminopyrrolidinyl 20b and the 7-diazabicyclo naphthyridine 18b are the most potent compounds in vitro and in vivo. Physicochemical data and acute toxicity are also discussed. Compound 18b, BMY 40062, exhibits the most favorable overall properties, considering in vitro and in vivo microbiological activity, its low toxicity, and pharmacokinetic profile, and was selected for clinical evaluation.