Dopamine/Serotonin Receptor Ligands. 16. Expanding Dibenz[d,g]azecines to 11- and 12-Membered Homologues. Interaction with Dopamine D1−D5 Receptors
journal contributionposted on 02.04.2020 by Christoph Enzensperger, Franziska K. U. Müller, Bärbel Schmalwasser, Petra Wiecha, Heidi Traber, Jochen Lehmann
Any type of content formally published in an academic journal, usually following a peer-review process.
Oxygenated 7-methyl-5,6,7,8,9,14-hexahydrodibenz[d,g]azecines are potent dopamine receptor antagonists, preferentially at D1/D5. We synthesized the hydroxylated, methoxylated, and chlorinated 11-membered and 12-membered homologues of these 10-membered heterocycles. Their affinities for the human cloned D1−D5 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 D1/D5 but also leads to a compound with a clozapine-like binding profile due to additional affinity for D4.