Patent Evaluation: Benzodioxan Antipsychotic Agents

Summary

Novelty: Novel aminophenoxyalkyl derivatives of benzodioxan are disclosed and are claimed to be antipsychotic, antidepressant and anxiolytic agents. They are useful in the treatment of multi-CNS disease states.

Biology: The effect of the compounds on the synthesis of dopamine was determined using the method of Walters (Naunyn-Schmiedeberg's Arch. Pharmacol. (1976) 296:5-14). The antipsychotic activity of these compounds was determined using the method of Martin (J. Pharmacol. Exp. Therap. (1984) 229:706-711). The affinity for the dopamine D₂ receptor was also assayed for the compounds using the method of Fields (Brain Res. (1977) 136:578). Affinity for the 5HT_1A receptor was determined by the method of Hall et al. (J. Neurochem. (1985) 44:1685). The specified compound gave 64% (limbic) and 66% (striatal) inhibition of 0.15 mg ip and receptor affinities (IC₅₀) of 51 nM (D₂) and 8 nM (5HT_1A). Results for nineteen compounds are presented in a table.

Chemistry: Synthesis of the compounds are described in nineteen examples. N-[3-(3-aminophenoxy)propyl]-2,3-dihydro-7-hydroxy-1,4-benzodioxin-2-metanamine is one of fifteen specifically claimed compounds.