Synthesis of previously inaccessible quinazolines and 1,4-benzodiazepines as potential anticonvulsants

A series of 4,6,7,8- tetrasubstituted 3,4- dihydroquinazolines , quinazolines, quinazolin -2-ones, 1,2,3,4- tetrahydroquinazolin -2-ones, and 5,7,8,9- tetrasubstituted 1,4-benzodiazepines have been synthesized by utilizing the Diels -Alder reaction between furan o-amino nitriles and various alkyl or aryl vinyl ketone dienophiles to obtain the anthranilic acid precursors. All of the newly synthesized target compounds were evaluated in mice for anticonvulsant activity. Pro- and anticonvulsant action was quantified by the timed intravenous pentylenetetrazol seizure threshold method. Selected compounds were also evaluated for benzodiazepine receptor binding properties and in vivo antagonist potential. Although the compounds lack potency, the data suggest that previously inaccessible substituted analogues may be useful to segregate the proconvulsant , anticonvulsant, and antagonist actions of benzodiazepines and quinazolines.