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  • Title: Synthesis and anticonvulsant activity of novel 2,6-diketopiperazine derivatives. Part 1: perhydropyrrole[1,2-a]pyrazines.
    Author: Dawidowski M, Herold F, Chodkowski A, Kleps J, Szulczyk P, Wilczek M.
    Journal: Eur J Med Chem; 2011 Oct; 46(10):4859-69. PubMed ID: 21862182.
    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), 6 Hz and pilocarpine-induced status prevention (PISP) tests, with ED(50) 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.
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