RESUMEN
A series of potential anticonvulsants have been synthesized. There are eight fluorobenzylamides and three chlorobenzylamides of isocyclic or heterocyclic acids. Two not halogenated benzylamides were also synthesized to compare the effect of halogenation. The aim of the research performed was to evaluate whether halogenation of the mother structure is able to improve its anticonvulsant activity. The compounds were tested in Anticonvulsant Screening Project (ASP) of Antiepileptic Drug Development Program (ADDP) of NIH. Compound 1 showed MES ED50 = 80.32 mg/kg, PI = 3.16. Compound 7 showed CKM ED50 = 56.72 mg/kg. Compound 8 showed MES ED50 = 34.23 mg/kg and scPTZ ED50 > 300 mg/kg, PI = 8.53.Compound 13 showed 6Hz ED50 = 78.96, PI = 3.37. The results indicate that fluorination does not improve activity, whereas chlorination in our experiment even reduces it.
Asunto(s)
Ácidos Heterocíclicos/síntesis química , Amidas/síntesis química , Anticonvulsivantes/síntesis química , Compuestos de Bencilo/síntesis química , Ácidos Heterocíclicos/farmacología , Amidas/farmacología , Animales , Anticonvulsivantes/farmacología , Compuestos de Bencilo/farmacología , Ratones , Relación Estructura-ActividadRESUMEN
A series of benzylamides of isocyclic and heterocyclic acids was synthesized and tested in Anticonvulsant Screening Project (ASP) of Antiepileptic Drug Development Program (ADDP) of NIH. Near all synthesized derivatives of heterocyclic acids showed activity. All obtained derivatives of mono- and bicyclic isocyclic acids were inactive. The power of action of heterocyclic acids derivatives seems does not depend upon kind of heteroatom (N, O or S). One of the compounds (2-furoic acid benzylamide (4)) appeared most promising. It showed in minimal clonic seizure (6Hz) test (ASP) in rats after i. p. administration: MES ED50 = 36.5 mg/kg, TOX TD50 = 269.75 mg/kg, and PI = 7.39.
Asunto(s)
Amidas/síntesis química , Amidas/farmacología , Anticonvulsivantes/síntesis química , Anticonvulsivantes/farmacología , Compuestos de Bencilo/síntesis química , Compuestos de Bencilo/farmacología , Convulsiones/prevención & control , Amidas/toxicidad , Animales , Anticonvulsivantes/toxicidad , Compuestos de Bencilo/toxicidad , Modelos Animales de Enfermedad , Estructura Molecular , Pilocarpina , Ratas , Convulsiones/inducido químicamente , Relación Estructura-ActividadRESUMEN
Qualitative and quantitative methods of analysis of three new amino-acid derivatives potential anticonvulsants of low neurotoxicity: picolinic acid benzylamide (1), nicotinic acid benzylamide (2) and isonicotinic acid benzylamide (3) were developed. Qualitative analysis includes characteristic reactions, chromatographic (TLC) investigations, IR and UV spectra interpretation. The quantitative analysis involves spectophotometric, chromatographic (HPLC) and acidimetric methods.
Asunto(s)
Anticonvulsivantes/análisis , Anticonvulsivantes/química , Compuestos de Bencilo/análisis , Compuestos de Bencilo/química , Cromatografía Líquida de Alta Presión/métodos , Niacina/análogos & derivados , Niacina/análisis , Niacina/química , Ácidos Picolínicos/análisis , Ácidos Picolínicos/química , Sensibilidad y Especificidad , Espectrofotometría/métodosRESUMEN
Qualitative and quantitative methods of analysis of two new amino acid derivatives, potential anticonvulsants of low neurotoxicity: N-acetyl-gamma-aminobutyric acid benzylamide (1) and N-melhyl-gamma-aminobutyric acid benzylamide (2) were developed. Qualitative analysis includes characteristic colour reactions, chromatographic (TLC) investigations, IR and UV spectra interpretation and quantitative analysis involves spectrophotometric, chromatographic (HPLC). acidimetric and argentomeric methods.