Microwave assisted synthesis of some hybrid molecules derived from norfloxacin and investigation of their biological activities

Norfloxacin was converted to 7-(4-amino-2-fluorophenyl)piperazin derivative (2) via the formation of nitro compound. The synthesis of the norfloxacin derivatives containing 1,3-thiazole or 1,3-thiazolidin moiety was performed from the reaction of 4-chlorophenacylbromide or ethyl bromoacetate with compounds 4-7 obtained starting from 2. 3-Fluoro-4-[4-(2-methoxyphenyl)piperazin-1-yl]aniline (14), 5-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-4-phenyl-4H-1,2,4-triazole-3-thiol (18) and {[4-(2-methoxy phenyl)piperazin-1-yl]methyl)-1,3,4-oxadiazol-2-thiol (19) were obtained starting from 1-(2-methoxyphenyl)piperazine by several steps. The treatment of hydrazide (16) with several aldehydes afforded N'-[(2-hydroxyphenyl)methylen]- (20), N'-[(3-hydroxy-4-methoxy phenyl)methylen]- (21) or N'-[1H-indol-3-ylmethylene]-2-[4-(2-methoxyphenyl)piperazin-1-yl]acetohydrazide (22). Then, compounds 14, 18, 19 and 22 were condensed with 7[4-(chloroacetyl)piperazin-1-yl]-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (3) that was obtained from norfloxacine. All newly synthesized compounds were screened for their antimicrobial activities and some of them exhibited excellent activity. Moreover, one compound was found to have antiurease activity. (C) 2013 Elsevier Masson SAS. All rights reserved.