title: 3-(4-(6-Fluoroalkoxy-3,4-dihydroisoquinoline-2(1H)-yl)cyclohexyl)-1H-indole-5-carbonitriles for SERT imaging: chemical synthesis, evaluation in vitro and radiofluorination.
abstract: Aminocyclohexyl indoles bind with high affinity and specificity toward the serotonin transporter (SERT). Based on this structural lead, we designed fluoroalkoxydihydroisoquinoline-cyclohexyl indole carbonitriles for future application as (18)F-labeled tracers for SERT imaging by PET. Six compounds, three pairs of cis- and trans-isomer derivatives, respectively, were synthesized and evaluated in vitro. The chemistry of the new compounds, their affinity and specificity data, the general route to the phenolic precursor for labeling, and the successful (18)F-fluoroalkylation of one pair of compounds are described herein.
authors.affiliation: Institut für Interdisziplinäre Isotopenforschung, Permoserstr. 15, D-04318 Leipzig, Germany. funke@iif-leipzig.de
authors.forename: Uta
authors.initials: U
authors.lastname: Funke
authors.forename: Steffen
authors.initials: S
authors.lastname: Fischer
authors.forename: Achim
authors.initials: A
authors.lastname: Hiller
authors.forename: Matthias
authors.initials: M
authors.lastname: Scheunemann
authors.forename: Winnie
authors.initials: W
authors.lastname: Deuther-Conrad
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinbach
mesh_terms: D002244:Carbon / Q000737:chemistry* / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002845:Chromatography / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002855:Chromatography, Thin Layer / Q000379:methods; D015195:Drug Design; D005462:Fluorine Radioisotopes / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007700:Kinetics; D026901:Membrane Transport Proteins / Q000378:metabolism; D008956:Models, Chemical; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry*
chemical_list: D005462:Fluorine Radioisotopes; D007211:Indoles; D026901:Membrane Transport Proteins; D009570:Nitriles; D011804:Quinolines; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D002244:Carbon