PYRROLIDINO ENAMINONES STRUCTURAL RELATED TO GYRASE INHIBITORS - SYNTHESIS, CYCLIZATION AND PHARMACOLOGICAL ACTIVITY

The synthesis and stereochemical characteristics of pyrrolidino enamin ones with structural analogy to quinolone antibacterial agents are rep orted. Retro-aldol reaction of the esters 7 is observed under all cond itions of hydrolysis, the enzyme catalyzed reaction also does not yiel d the corresponding acids. In contrast to clinically used quinolones e xemplary tests with monocyclic esters of type 7 and the tricyclic deri vative 10 indicate low or no antibacterial activity. Additionally to t he lack of the carboxylic acid function the enaminones 7 differ from q uinolones in stereochemical demands and the electronic situation of th e phenyl substituents of 10, respectively possibly preventing the form ation of a co-operative tetrametric system between compounds and DNA b ases.