Synthesis, structure, and antibacterial activity of 4-imino-1,4-dihydrocinnoline-3-carboxylic acid and 4-oxo-1,4-dihydrocinnoline-3-carboxylic acid derivatives as isoteric analogues of quinolones

Chemical modification of cinnoxacin was studied with the aim of improving its antibacterial activity and spectrum. A series of 4-imino-1,4-dihydrocinnoline-3-carboxylic acid derivatives was synthesized and their in vitro antibacterial activity was evaluated. These derivatives were designed as isosteric analogues of fluoroquinolones and are characterized by the presence of an imine group instead of an oxo group at the 4-position and a nitrogen atom in position 2. The crystal structure of one analogue determined by X-ray diffraction shows the dipolar form of the compound in the solid state. The in vitro antibacterial activity of the synthesized compounds against Gram-positive and Gram-negative bacteria was examined. The MIC of the most active compounds lies in the range of the first generation of quinolones such as nalidixic acid. The compounds with dichlorobenzyl substituent show enhanced activity against Gram-positive bacteria.