title: Synthesis and receptor binding properties of 2beta-alkynyl and 2beta-(1,2,3-triazol)substituted 3beta-(substituted phenyl)tropane derivatives.
abstract: A series of 2beta-alkynyl and 2beta-(1,2,3-triazol)substituted 3beta-(substituted phenyl)tropanes were synthesized and evaluated for affinities at dopamine, serotonin, and norepinephrine membrane transporters using competitive radioligand binding assays. All tested compounds were found to exhibit nanomolar or subnanomolar affinity for the dopamine transporter (DAT). One of the most potent and selective compounds in the series was 3beta-(4-chlorophenyl)-2beta-(4-nitrophenylethynyl)tropane (10c) that possessed an IC(50) value of 0.9nM at the DAT and K(i) values of 230nM and 620nM at the norepinephrine transporter (NET) and serotonin transporter (5-HTT), respectively.
authors.affiliation: Organic and Medicinal Chemistry, Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709-2194, USA.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Jin
authors.forename: Hernán A
authors.initials: HA
authors.lastname: Navarro
authors.forename: F Ivy
authors.initials: FI
authors.lastname: Carroll
mesh_terms: D001667:Binding, Competitive / Q000187:drug effects; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D008968:Molecular Conformation; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000187:drug effects*; D011869:Radioligand Assay; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D014326:Tropanes