title: Dibenzazecine scaffold rebuilding--is the flexibility always essential for high dopamine receptor affinities?
abstract: The moderately flexible 7-methyl-5,6,7,8,9,14-hexahydrodibenz[d,g]azecines are known to be potent dopamine receptor antagonists, whereas the corresponding rigid dibenzo[d,g]quinolizines are inactive. We built the scaffolds of dibenzo[c,g], [c,f] and [d,f]azecines and together with their ring closed, more rigid precursors, evaluated the affinities for the human D(1)-D(5) receptors (radioligand binding) as well as the functionalities (calcium assay) and thus investigated the influence of annelation and conformative flexibility of these compounds on their affinity for human cloned dopamine receptors.
authors.affiliation: Institut für Pharmazie, Lehtuhl für Pharmazeutische/Medizinische Chemie, Friedrich-Schiller-Universität Jena, Philosophenweg 14, 07743 Jena, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Schulze
authors.forename: Franziska K U
authors.initials: FK
authors.lastname: Müller
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Mason
authors.forename: Helmar
authors.initials: H
authors.lastname: Görls
authors.forename: Jochen
authors.initials: J
authors.lastname: Lehmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Enzensperger
mesh_terms: D002118:Calcium; D003001:Cloning, Molecular; D018492:Dopamine Antagonists / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D008968:Molecular Conformation; D018583:Pliability; D011485:Protein Binding; D011807:Quinolizines / Q000737:chemistry*; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D018492:Dopamine Antagonists; D006571:Heterocyclic Compounds; D011807:Quinolizines; D011954:Receptors, Dopamine; D002118:Calcium