Dopamine/Serotonin Receptor Ligands. 13: Homologization of a Benzindoloazecine-Type Dopamine Receptor Antagonist Modulates the Affinities for Dopamine D1−D5 Receptors

Enlarging the 10-membered ring of 7-methyl-6,7,8,9,14,15-hexahydro-5H-indolo[3,2-f][3]benzazecine (1, LE 300) yielded two homologue antagonists. Their affinities and inhibitory activities at D(1)-D(5) receptors were measured by radioligand binding experiments and a functional Ca(2+) assay. Compared to 1, phenylpropyl homologue 3 was superior in selectivity and affinity for the D(5) subtype (K(i) = 0.6 nM), whereas the affinity of the indolylpropyl homologue 2 for all subtypes decreased. Compounds 2, 3, 10, 11, 17, and 18 are derivatives of novel heterocyclic ring systems.