Synthesis and potential anticonvulsant activity of new 5,5-cyclopropanespirohydantoin derivatives

Abstract

In this study, sixteen new 5,5-cyclopropanespirohydantoin derivatives were synthesized and tested for anticonvulsant activity using maximal electroshock (MES), subcutaneous pentylenetetrazole screens. Their neurotoxicity was determined by the rotarod test. Two compounds 7f and 7n showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 7f showed the MES-induced seizures with ED 50 value of 8.5 mg/kg and TD 50 value of 381.7 mg/kg after intraperitoneally injection to mice, which provided compound 7f with a protective index (TD 50 /ED 50 ) of 44.9 in the MES test.

A new synthesis of 3-arylideneamino- and 3-alkylideneamino-substituted hydantoins

“…However, in contrast to 1-aminohydantoins, their 3-amino analogues are much less studied. Described syntheses of 3-aminohydantoin derivatives from acyclic precursors generally involve formation of one or two C-N bonds (e.g., N3-C4 [8,[12][13][14][15], C2-N3 [16][17][18], both N1-C2 and N3-C4 [19][20][21][22][23], both N1-C5 and N3-C4 bonds [24]). These compounds are also prepared using recyclizations of certain heterocyclic compounds [25][26][27][28][29][30][31][32][33].…”