Benzodiazepine receptor ligands. Synthesis and preliminary pharmacological evaluation of 2-aminoalkyl-8-chloro- and 2-aryl-1,2,4-triazolo[3,4-a]phthalazine-3(2H)-ones.

Some 2-aminoalkyl-8-chloro- and 2-aryl-1,2,4-triazolo[3,4-a]-phthalazine-3-(2H)-ones were synthesized and preliminarily tested in vitro and in vivo as potential benzodiazepine-receptor (BZRs) ligands. 2-Aryl-1,2,4-triazolo[3,4-a]-phthalazine-3(2H)-ones displaced in vitro 3H-diazepam (3H-DZ) from rat brain specific binding sites with Ki (nM) comparable to DZ and chlordiazepoxide used as reference compounds. The specific binding of the triazolones of this study was not enhanced in vitro by 4-aminobutyric acid (GABA) and in vivo they did not show any activity in counteracting the pentylenetetrazole (PTZ) induced convulsions (mice). One of these compounds (IV a) antagonized the effects of DZ in the bicuculline (BIC) induced convulsions test (mice) and the DZ induced muscle relaxant effects in the horizontal wire test.