Pyrrolidino enaminones structural related to gyrase inhibitors: synthesis, cyclization and pharmacological activity

The synthesis and stereochemical characteristics of pyrrolidino enaminones with structural analogy to quinolone antibacterial agents are reported. Retro-aldol reaction of the esters 7 is observed under all conditions of hydrolysis, the enzyme catalyzed reaction also does not yield the corresponding acids. In contrast to clinically used quinolones exemplary tests with monocyclic esters of type 7 and the tricyclic derivative 10 indicate low or no antibacterial activity. Additionally to the lack of the carboxylic acid function the enaminones 7 differ from quinolones in stereochemical demands and the electronic situation of the phenyl substituents of 10, respectively possibly preventing the formation of a co-operative tetrametric system between compounds and DNA bases.