Solution-phase parallel synthesis and evaluation of anticonvulsant activity of N-substituted-3,4-dihydroisoquinoline-2(1H)-carboxamides.
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.
Gitto
Rosaria
R
Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy. rgitto@pharma.unime.it
Pagano
Benedetta
B
Citraro
Rita
R
Scicchitano
Francesca
F
De Sarro
Giovanbattista
G
Chimirri
Alba
A
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008811:Mice, Inbred DBA; D012640:Seizures / Q000517:prevention & control
D000927:Anticonvulsants; C109852:G 1616; D007546:Isoquinolines