title: RECEPTOR AFFINITY AND PHOSPHODIESTERASES 4B AND 10A ACTIVITY OF OCTAHYDRO- AND 6,7-DIMETHOXY-3,4-DIHYDRO- ISOQUINOLIN-2(1H)-YL-ALKYL DERIVATIVES OF IMIDAZO- AND PYRIMIDINO[2,1-f]PURINES.
abstract: A series of octahydro- and 6,7-dimethoxy-3,4-dihydro- isoquinolin-2(1H)-yl-alkyl derivatives of imidazo- and pyrimidino[2,1-f]purines were synthesized and biologically evaluated in in vitro competition binding experiments for serotonin 5-HT(1A), 5-HT(6), 5-HT(7), and dopamine D2 receptors and inhibitory potencies for phosphodiesterases - PDE4B1 and PDE10A. The structure-activity relationships allowed to determine the structural features responsible for receptor and enzyme activity. Compound 5 (8-(4-(6,7-dimethoxy-3,4-dihydroiso- quinolin-2(1H)butyl)1,3-dimethyl-H-imidazo[2,1-f]purine-2,4(3H,8H)-dione) could be regarded as promising structure for further modification and detailed mechanistic study for obtained hybrid ligands.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zagórska
authors.forename: Beata
authors.initials: B
authors.lastname: Gryzło
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Satała
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Bojarski
authors.forename: Monika
authors.initials: M
authors.lastname: Głuch-Lutwin
authors.forename: Barbara
authors.initials: B
authors.lastname: Mordyl
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kazek
authors.forename: Maciej
authors.initials: M
authors.lastname: Pawłowski
mesh_terms: D001667:Binding, Competitive; D057809:HEK293 Cells; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008024:Ligands; D015394:Molecular Structure; D058988:Phosphodiesterase 4 Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011744:Pyrimidinones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: C581293:DRD2 protein, human; D007093:Imidazoles; D008024:Ligands; D058988:Phosphodiesterase 4 Inhibitors; D011744:Pyrimidinones; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D010727:Phosphoric Diester Hydrolases