Synthesis of pyrazoloquinolone rigid analogs

Abstract

A coplanarity between C-3 carboxylic acid and C-4 carbonyl has been proposed to be one of the structural requirements of the quinolones for binding to the receptor. The rigid analogs of quinolone, pyrazolo (4,3-c) quinolin-3-one derivatives, were designed and synthesized as potential antibacterial agents. Pyrazoloquinolones have been prepared via 4 steps. 1) Synthesis of quinoline ring was achieved by thermal cyclization of diethyl ethoxymethylenemalonate and aniline. 2) 4-Hydroxyquinoline derivatives were chlorinated with thionyl chloride to afford 4-chloroquinoline intermediates. 3) Pyrazoloquinolone derivatives were obtained by the reaction of 4chloroquinoline intermediates with phenylhydrazine and hydrazine at high temperature and in alkali condition, respectively. 4) Pyrazolo (4,3-c) quinolin-3-one derivatives were N-ethylated with ethyl iodide and sodium hydride. The reaction of piperazine with the two derivatives of pyrazoloquinolones, 7-chloro-8-fluoro-5-ethyl-2-aryl pyrazolo (4,3-c) quinolin-3-one and 7-chloro-8-fluoro-5-ethyl-2H-pyrazolo (4,3-c) quinolin3-one, yielded the 8-(1-piperazinyl) derivatives.