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.
Dannhardt
G
G
Institute of Pharmacy, Johannes-Gutenberg-University Mainz, Germany.
Bauer
A
A
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D018360:Crystallography, X-Ray; D003500:Cyclization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D008968:Molecular Conformation; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D011759:Pyrrolidines; D059005:Topoisomerase II Inhibitors