SEARCH FOR NEW ANTICONVULSANT COMPOUNDS .2. STRUCTURE-ACTIVITY RELATIONSHIP STUDIES OF NEW N-SUBSTITUTED AMIDES OF ALPHA-PIPERAZINE-GAMMA-HYDROXYBUTYRIC ACID AS ACTIVE ANTICONVULSANTS

In a search for new anticonvulsants, two series of compounds, viz. der ivatives of N-benzylamides of alpha-(4-phenylpiperazine)-gamma-hydroxy butyric acid (A) and derivatives of N-benzylamides of alpha-(4-benzylp iperazine)-gamma-hydroxybutyric acid (B), were investigated. These ami des were obtained by aminolysis of 3-(4-phenyl-, or 4-benzylpiperazine )-tetrahydrofuran-2-one with primary arylal- kylamines (i.e. 2-phenyle thylamine and 2,3,4-substituted derivatives of benzylamine). Prelimina ry pharmacological tests, a maximal electroshock (MES) and a subcutane ous metrazole (scMet), and a rotorod toxicity assay were employed. All compounds displayed anticonvulsant activity at range of doses 100-300 mg/kg in the MES screens. In order to point to some structural featur es correlating with the MES anticonvulsant activity crystal structure analysis followed by conformational analysis was carried out on two re presentative compounds of series A and B.