In our previous studies we identified several isoquinoline derivatives displaying potent anticonvulsant effects in different animal models of epilepsy. With the aim to exploit the main structure-activity relationships (SAR) for this class of compounds we planned a solution-phase parallel synthesis (SPPS) of new N-substituted-3,4-dihydroisoquinoline-2(1H)-carboxamides exploring the effect of introduction of different (cyclo)alkyl groups at carboxamide moiety linked to N-2 atom of isoquinoline scaffold. The pharmacological effects were evaluated against audiogenic seizures in DBA/2 mice and, even if some new derivatives were more active than valproate, the designed modifications did not improve the anticonvulsant efficacy with respect to their precursors.