title: N-Arylalkyl-2-azaadamantanes as cage-expanded polycarbocyclic sigma (σ) receptor ligands.
abstract: A series of racemic N-arylalkyl-2-azaadamantan-1-ols (9-15) and the corresponding deoxygenated, achiral N-arylalkyl-2-azaadamantanes (23-29) were synthesized and screened in competition binding assays against a panel of CNS targets. Adamantyl hemiaminals 9-15 displayed generally low affinity for both σ(1) (K(i) values= 294-1950 nM) and σ(2) receptors (K(i) values=201-1020 nM), and negligible affinity for 42 other CNS proteins. Deoxygenation of 9-15 to give the corresponding achiral azaadamantanes 23-29 greatly improved affinity for σ(1) (K(i) values=8.3-239 nM) and σ(2) receptors (K(i) values=34-312 nM).
authors.affiliation: School of Chemistry, The University of Sydney, Sydney NSW 2006, Australia.
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Banister
authors.forename: David T
authors.initials: DT
authors.lastname: Yoo
authors.forename: Sook Wern
authors.initials: SW
authors.lastname: Chua
authors.forename: Jinquan
authors.initials: J
authors.lastname: Cui
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mach
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D015394:Molecular Structure; D017480:Receptors, sigma / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D017480:Receptors, sigma; D000218:Adamantane