title: Substituted diphenyl sulfides as selective serotonin transporter ligands: synthesis and in vitro evaluation.
abstract: A series of diphenyl sulfide derivatives substituted at the 1-, 2'-, and 4'-positions has been synthesized and evaluated for their in vitro affinities at the dopamine, serotonin (SERT), and norepinephrine transporters. The examination of K(i) values revealed that most of these derivatives have high affinity and selectivity for the SERT. Moreover, substitutions at these positions differently influence the SERT binding: (i) The nature of the substituent linked at the 1-position critically influences the SERT affinity. (ii) Functions containing heteroatom at the 2'-position afford compounds with high SERT affinity. (iii) The nature of the substituent at the 4'-position slightly influences the SERT affinity whereas steric effect markedly decreases the SERT affinity. From this series, the most SERT selective derivatives (such as 8b, 8c, and 8g) are now evaluated for their potential as positron emission tomography imaging agents when labeled with carbon-11.
authors.affiliation: INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 31 Avenue Monge, 37200 Tours, France. emond@univ-tours.fr
authors.forename: Patrick
authors.initials: P
authors.lastname: Emond
authors.forename: Johnny
authors.initials: J
authors.lastname: Vercouillie
authors.forename: Robert
authors.initials: R
authors.lastname: Innis
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chalon
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mavel
authors.forename: Yves
authors.initials: Y
authors.lastname: Frangin
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Besnard
authors.forename: Denis
authors.initials: D
authors.lastname: Guilloteau
mesh_terms: D001665:Binding Sites / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003287:Contrast Media / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D013379:Substrate Specificity; D013440:Sulfides / Q000138:chemical synthesis* / Q000494:pharmacology; D014055:Tomography, Emission-Computed
chemical_list: D002352:Carrier Proteins; D003287:Contrast Media; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides; D012701:Serotonin