title: Solution-phase parallel synthesis and evaluation of anticonvulsant activity of N-substituted-3,4-dihydroisoquinoline-2(1H)-carboxamides.
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.
authors.affiliation: Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy. rgitto@pharma.unime.it
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gitto
authors.forename: Benedetta
authors.initials: B
authors.lastname: Pagano
authors.forename: Rita
authors.initials: R
authors.lastname: Citraro
authors.forename: Francesca
authors.initials: F
authors.lastname: Scicchitano
authors.forename: Giovanbattista
authors.initials: G
authors.lastname: De Sarro
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
mesh_terms: 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
chemical_list: D000927:Anticonvulsants; C109852:G 1616; D007546:Isoquinolines