PYRROLOBENZODIAZEPINES WITH ANTINOCICEPTIVE ACTIVITY - SYNTHESIS AND PHARMACOLOGICAL ACTIVITIES

The synthesis of some N-[2-(1H-pyrrol-1-yl)benzyl] arylacetamides and new 4-arylmethyl-5,6-dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepines, as their conformationally restricted analogues is reported. The reduction of arylacetamides and N-methylation of pyrrolobenzodiazepines led to the corresponding N-[2-(1H-pyrrol-1-yl)benzyl]arylethylamines and the 4-arylmethyl-5-methyl-5,6-dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepines, respectively. The new compounds were subjected to pharmacological tests for evaluation of antinociceptive effects. Neurobehavioural assays were also carried out on selected compounds to acquire data on neurotoxicity. Among the derivatives tested, arylacetamides 7b and 7e and 4-(4-methoxybenzyl)-5-methyl-5,6-dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepine 10d were the most active derivatives in antinociceptive assays, showing high significance in both hot-plate and acetic-acid-induced writhing tests in mice without sedative or myorelaxant effects.