title: Dopamine/serotonin receptor ligands. 13: Homologization of a benzindoloazecine-type dopamine receptor antagonist modulates the affinities for dopamine D(1)-D(5) receptors.
abstract: 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.
authors.affiliation: Institut für Pharmazie, Lehrstuhl für Pharmazeutische/Medizinische Chemie, Friedrich-Schiller-Universität Jena, Philosophenweg 14, D-07743 Jena, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Enzensperger
authors.forename: Jochen
authors.initials: J
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D065127:Dopamine D2 Receptor Antagonists; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors; D050638:Receptors, Dopamine D4 / Q000037:antagonists & inhibitors; D050641:Receptors, Dopamine D5 / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
chemical_list: C409874:7-methyl-6,7,8,9,14,15-hexahydro-5H-benz(d)indolo(2,3-g)azecine; D065127:Dopamine D2 Receptor Antagonists; D006576:Heterocyclic Compounds, 4 or More Rings; D007211:Indoles; D017447:Receptors, Dopamine D1; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5; D002118:Calcium