title: Synthesis and pharmacological characterization of new tetrahydrofuran based compounds as conformationally constrained histamine receptor ligands.
abstract: A series of tetrahydrofuran based compounds with a bicyclic core that provides conformational restriction were synthesized and investigated by radioligand displacement studies and functional [(35)S]GTPγS binding assays at the human histamine receptor (hHR) subtypes. The amines and ((1S,3R,5S,6R)- and ((1S,3S,5S,6R)-3-(1H-imidazol-5-yl)-2-oxabicyclo[3.1.0]hexan-6-yl)methanamine), exhibited submicromolar Ki values at the hH3R with 10-fold higher affinities than their corresponding (6S)-epimers and 25- and >34-fold selectivity over the hH4R, respectively. Both compounds act as neutral antagonists at the hH3R with KB values of 181 and 32 nM, respectively. The cyanoguanidines of the imidazole series and the oxazole analogues turned out to be inactive at all hHR subtypes.
authors.affiliation: Institut für Organische Chemie, Universität Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Bodensteiner
authors.forename: Paul
authors.initials: P
authors.lastname: Baumeister
authors.forename: Roland
authors.initials: R
authors.lastname: Geyer
authors.forename: Armin
authors.initials: A
authors.lastname: Buschauer
authors.forename: Oliver
authors.initials: O
authors.lastname: Reiser
mesh_terms: D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D011968:Receptors, Histamine / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D005663:Furans; D008024:Ligands; D011968:Receptors, Histamine; C018674:tetrahydrofuran