Design, synthesis and biological evaluation of novel dicarbonylalkyl piperazine derivatives as neuroprotective agents

In the search of novel neuroprotective agents with higher potency than our previously identified antiischemic stroke drug candidate 1, a series of novel dicarbonyl piperazine derivatives were synthesized and evaluated on their neuroprotective activity via oxygen–glucose deprivation test in the neuron-like PC12 cells, hypoxia tolerance model in mice and focal cerebral ischemia model in rats. The result obtained indicated that compounds 7f, 7k and 7o, exhibited neuroprotective activity. Particularly,compound 7o containing 2,5-dimethylpiperazin moiety, showed prolonged life time of mice and reduced cerebral infarction of rats, which provided a potential candidate for the development of neuroprotective agents.