Solution-phase parallel synthesis and evaluation of anticonvulsant activity of N-substituted-3,4-dihydroisoquinoline-2(1H)-carboxamides.

Eur J Med Chem, 2009/3;44(3):1349-54.

Gitto R[1], Pagano B, Citraro R, Scicchitano F, De Sarro G, Chimirri A

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PMID: 18406016DOI: 10.1016/j.ejmech.2008.02.025

Impact factor: 7.088

Abstract
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.
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