Studies on biologically Active Halogenated Compounds. IV. Synthesis and Antibacterial Activity of Fluorinated Quinoline Derivatives

Polyfluorinated derivatives of 1-alkyl-1, 4-dihydro-7-methyl-4-oxoquinoline-3-carboxylic acids were synthesized and examined for antibacterial activites in vitro. Among the N-substituents, the strength of antibacterial activity of the derivatives was in the order : CH2CH2F>CH2CH3>CH2CF3>CHF2. Introduction of two fluorine atoms at the 6 and 8 positions of the skeleton (21a, b) led to high activity, but substitution of the 7-methyl group (20, 21, 25) with a fluoromethyl group (40, 41, 48) led in general to reduced activity. Thus, 6, 8-difluoro-1, 4-dihydro-1-(2-fluoroethyl)-7-methyl-4-oxoquinoline-3-carboxylic acid (21b) showed the highest activity, almost equal to that of oxolinic acid.