Dopamine/serotonin receptor ligands. 9. Oxygen-containing midsized heterocyclic ring systems and nonrigidized analogues. A step toward dopamine D5 receptor selectivity

Eleven-membered heterocycles (dibenz[g,j]-1-oxa-4-azacycloundecenes) and open-chain analogues were synthesized and investigated for affinities to human Dopamine Receptor subtypes. The moderately rigidized rings displayed nanomolar and subnanomolar Ki values at D1-like receptors with a significant D1 to D2 and a slight D5 to D1 selectivity. The open-chain analogues showed lower affinities but significant D1 to D2 selectivities. Compound 3 (Ki(D5) = 0.57 nmol) showed antagonistic or inverse agonistic binding characteristics in a functional CA assay.