Dopamine/Serotonin receptor ligands. 16. expanding dibenz[d,g]azecines to 11- and 12-membered homologues. Interaction with dopamine D-1-D-5 receptors

摘要

Oxygenated 7-methyl-5,6,7,8,9,14-hexahydrodibenz[d,g]azecines are potent dopamine receptor antagonists, preferentially at D-1/D-5. We synthesized the hydroxylated, methoxylated, and chlorinated 11-membered and 12-membered homologues of these 10-membered heterocycles. Their affinities for the human cloned D-1-D-5 receptors (radioligand binding) and functionalities (calcium assay) were measured. Enlarging the dibenzazecines to the corresponding dibenzazacycloundecenes and dibenzazacyclododecenes generally maintains the high antagonistic affinity for D-1/D-5 but also leads to a compound with a clozapine-like binding profile due to additional affinity for D-4.