Synthesis and anticonvulsant activity of novel 2,6-diketopiperazine derivatives. Part 1: Perhydropyrrole[1,2-a]pyrazines

Abstract: A number of novel pyrrole[1,2-a]pyrazine derivatives were synthesized and evaluated in in vivo animal models of epilepsy. Among them, several compounds displayed promising seizure protection in the maximal electroshock seizure (MES), subcutaneous metrazol seizure (scMET), 6Hz and pilocarpine-induced status prevention (PISP) tests, with ED50 values comparable to the reference anticonvulsant drugs (AEDs). A critical influence of the stereochemistry and conformational preferences of the pyrrole[1,2-a]pyrazine core on in vivo pharmacological activity was observed. The mechanism of the anticonvulsant action of the agents synthesized is most probably not via inhibition of the voltage-dependent sodium (Na+) currents. [Copyright &y& Elsevier]