Synthesis,biological evaluation and Structure Activity Relationships (SARs) study of 8-(substituted)aryloxycaffeine

A series of 8-(substituted)aryloxycaffeine were prepared from 8-bromocaffeine and (substituted)phenols by modified Ullmann reaction. In vitro antibacterial activity, inhibitory activity on topoisomerase II and pharmacological activities were evaluated for the synthesized 8-(substituted)aryloxycaffeine. Among the synthesized compounds, 8-(5-chloropyridin-3-yloxy)caffeine (3k) showed strong inhibitory activity (MIC = 15.6 μg/mL) against the tested gram negative (−) bacteria Salmonella enteritidis. 8-(quinolin-8-yloxy)caffeine (3g) showed the strongest inhibitory activity against topoisomerase II. And the compounds 8-(6-methylpyridin-2-yloxy)caffeine (3j) and 8-(3-chloro-6-(trifluoromethyl)pyridin-2-yloxy)caffeine (3m) showed analgesic effect without the central nervous system stimulation.