RESUMO
The synthesis of some 1,3- and 1,2- disubstituted [1]benzopyrano-pyrrol-4-ones is reported as well as their benzodiazepine receptor affinity, as measured by the ability to displace [3H]flunitrazepam from its specific central binding. The structure-activity relationships on the whole series of disubstituted [1]benzopyrano-pyrrol-4-ones show the importance of the presence of the 1-aryl substituent and the size limitation of the 3-substituent. The size of the latter seems also to be important for the "in vitro" efficacy.
Assuntos
Benzopiranos/síntese química , Pirróis/síntese química , Receptores de GABA-A/efeitos dos fármacos , Animais , Benzopiranos/farmacologia , Ligação Competitiva/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Bovinos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Fenômenos Químicos , Físico-Química , Flunitrazepam/metabolismo , Técnicas In Vitro , Ligantes , Pirróis/farmacologia , Relação Estrutura-Atividade , Ácido gama-Aminobutírico/metabolismoRESUMO
The synthesis of a series of 8-substituted 1,4-dihydro-1-aryl-3-methyl-[1]benzopyrano[3,4-d]pyrazol-4-ones (series 7) 2,4-dihydro-2-aryl-3-methyl[1]benzopyrano[4,3-c]pyrazol-4-ones (series 8) is reported. Compounds of series 7 and 8 were tested for their ability to displace [3H]flunitrazepam from bovine brain membranes and for their in vitro biological activity. The results allowed some conclusions to be drawn about the structural requirements of the benzodiazepine recognition site within this class of unusual ligands.
