title: ORL1 receptor ligands: structure-activity relationships of 8-cycloalkyl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-ones.
abstract: We have investigated 8-cycloalkyl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-o nes as ligands for the ORL1 receptor. These unsophisticated, achiral compounds show remarkable affinity for the ORL1 receptor. Optimizing for selectivity we show that the maximum of affinity and selectivity versus the other opioid receptors is achieved for 8-cyclodecyl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-o ne 2e and 8-(cis-4-isopropyl-cyclohexyl)-1-phenyl-1,3,8-triaza-spiro[4.5] decan-4-one 2q. The identified compounds (2e, 2q) are more or less equipotent to the natural ligand itself, both in the binding assay and in the functional GTPgammaS assay.
authors.affiliation: Pharma Division, PRBC, F. Hoffmann-La Roche Ltd., Basel, Switzerland. stephan.roever@roche.com
authors.forename: S
authors.initials: S
authors.lastname: Röver
authors.forename: J
authors.initials: J
authors.lastname: Wichmann
authors.forename: F
authors.initials: F
authors.lastname: Jenck
authors.forename: G
authors.initials: G
authors.lastname: Adam
authors.forename: A M
authors.initials: AM
authors.lastname: Cesura
mesh_terms: D002460:Cell Line; D006801:Humans; D008024:Ligands; D011957:Receptors, Opioid / Q000378:metabolism*; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry* / Q000494:pharmacology*; D000094942:Nociceptin Receptor
chemical_list: D008024:Ligands; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D014227:Triazines; D000094942:Nociceptin Receptor; C000722283:OPRL1 protein, human