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The syntheses of several 1-aryl-4-(arylpyridylmethyl)piperazines (4) and their affinities for dopamine D(2) and serotonin 5-HT(1A) receptors are described. The compounds were evaluated both in vitro and in vivo, resulting in the identification of the drug candidate SLV313 (4e) with equipotent and full D(2) receptor antagonism and 5-HT(1A) receptor agonism. Minor structural modifications in SLV313 revealed the possibility of designing compounds possessing varying degrees of partial agonism on one or both target receptors.

chemical and pharmaceutical bulletin/chemical and pharmaceutical bulletin

SAR Study of 1-Aryl-4-(phenylarylmethyl)piperazines as Ligands for Both Dopamine D2 and Serotonin 5-HT1A Receptors Showing Varying Degrees of (Ant)agonism. Selection of a Potential Atypical Antipsychotic