PROTEIN-BINDING IN A CONGENERIC SERIES OF ANTIBACTERIAL QUINOLONE DERIVATIVES

The extent of plasma protein binding has been determined in a series o f gyrase inhibitors characterised either by a varying substitution on the phenyl ring in position N1 or by an increasing alkyl chain at the nitrogen N4' of the piperazine moiety. It was tried to derive quantita tive structure activity relationships. Especially substituents at the m-position of the N1-phenyl ring were found to influence the extent of protein binding; an optimum of size could be determined. The increase of the alkyl group at the outer piperazine nitrogen which is combined with an augmented lipophilicity resulted in an increase in the degree of protein binding. So it can be concluded that the NI-phenyl ring as well as the piperazine ring take part in the interaction with the pla sma protein. Both substituents can be used to regulate the extent of p rotein binding in new gyrase inhibitors. (C) 1998 Elsevier Science B.V . All rights reserved.