Design, synthesis and anticonvulsant activity evaluation of 7-substituted-4H-[1,2,4]triazino[3,4-a]phthalazin-4-one derivatives

Abstract

Neste estudo, uma nova série de derivados de 4H- [1,2,4]triazina [3,4-a]ftalazin-4-ona substituídos em C-7 foi sintetizada como potenciais agentes anticonvulsivantes. Suas atividades anticonvulsivantes foram avaliadas pelo teste do eletrochoque máximo (MES), e suas neurotoxicidades, pelo teste "rotarod" de neurotoxicidade. Os resultados farmacológicos mostraram que a 7-hexiloxi-4H-[1,2,4]triazina[3,4-a]ftalazin-4-ona, 4e, foi a mais potente, com dose efetiva (ED 50 ) de 6,6 mg kg -1 e dose tóxica mediana (TD 50 ) de 39,4 mg kg , providing a protective index (PI=TD 50 /ED 50 ) value of 6.0.

Synthesis and Studies on the Anticonvulsant Activity of 5-alkoxy-[1,2,4]triazolo[4,3-a]pyridine Derivatives

“…The precipitate was fi ltered and washed with petroleum ether, then kept below 0 °C. The resulting crude compound was purifi ed by recrystallization in EtOH [ 8 ] .…”

“…The mixture was stirred for 2 h at room temperature to obtain the acid intermediate. The mixture was then evaporated under reduced pressure and the acid intermediate was reacted byrefl uxing in DMF for 3 h. The solution was evaporated to dryness and the oily residue was fi ltered on a silica gel chromatographic column (ethyl acetate) to give a light yellow or white solid [ 8 ] . Yield = 87 %.…”

“…2. 2,6-Dichloropyridine reacted with hydrazine hydrate in ethanol to aff ord compound 1[ 8 ] . In a next step, compound 1 reacted with formic acid in ethanol to obtain compound 2 , which in turn reacted with the appropriate alcohol or substituted phenol to yield the target compounds 3a-3 s[9 , 10 ] .…”