title: Trishomocubane as a scaffold for the development of selective dopamine transporter (DAT) ligands.
abstract: In our continued exploration of trishomocubane derivatives with central nervous system (CNS) activity, N-arylalkyl-8-aminopentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecanes (10-13) displaying affinity for the sigma (σ) receptor were also found, in several cases, to interact with the dopamine transporter (DAT). Compound 12 was identified as the first trishomocubane-derived high affinity DAT ligand (K(i) = 1.2 nM), with greater than 8300-fold selectivity over the monoamine transporters NET and SERT, and only low to moderate affinity for σ(1) and σ(2) receptors.
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: Iman A
authors.initials: IA
authors.lastname: Moussa
authors.forename: Corinne
authors.initials: C
authors.lastname: Beinat
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Reynolds
authors.forename: Paolo
authors.initials: P
authors.lastname: Schiavini
authors.forename: William T
authors.initials: WT
authors.lastname: Jorgensen
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
mesh_terms: D000473:Alkanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001596:Benzylamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000473:Alkanes; D001596:Benzylamines; D001952:Bridged-Ring Compounds; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008024:Ligands; D050484:Norepinephrine Plasma Membrane Transport Proteins; D017480:Receptors, sigma; D050486:Serotonin Plasma Membrane Transport Proteins; C022884:undecane