PYRROLOBENZODIAZEPINES WITH ANTINOCICEPTIVE ACTIVITY - SYNTHESIS AND PHARMACOLOGICAL ACTIVITIES

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