title: Technetium(V) and rhenium(V) complexes for 5-HT2A serotonin receptor binding: structure-affinity considerations.
abstract: Starting from the lead structure of ketanserin, a prototypic serotonin (5-HT) antagonist, new oxotechnetium(V) and oxorhenium(V) complexes were synthesized that are able to compete with [3H]ketan-serin in receptor-binding assays. To imitate organic 5-HT2 receptor ligands, fragments of ketanserin were combined with chelate moieties. Neutral compounds of the general formula [MOL1L2] (M = Tc, Re; L1 = HS-CH2CH2-S-CH2CH2-SH, N-(2-mercaptophenyl)salicylideneimine, N-(2-mercaptoethyl)-salicylideneimine, 3-(2-([N,N-bis(2-mercapto-S-ethyl)]-amino)ethyl)-2,4-(1H, 3H)-quinazolinedione and L2 = HS-R with R = subst. alkyl) were prepared by common action of a Tc(V) or Re(V) precursor with a mixture of equimolar amounts of a tridentate ligand L1 and a monodentate thiolate L2 bearing fragments of the lead structure. Lipophilic complexes consisting of a small S4 thiolate/thioether chelate unit, protonable nitrogen-containing spacer, and simple benzyl moiety significantly inhibited the specific binding of [3H]ketan-serin with IC50 values between 10 and 50 nM.
authors.affiliation: Forschungszentrum Rossendorf E.V., Institut Für Bioanorganische und Radiopharmazeutische Chemie, Dresden, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Johannsen
authors.forename: M
authors.initials: M
authors.lastname: Scheunemann
authors.forename: H
authors.initials: H
authors.lastname: Spies
authors.forename: P
authors.initials: P
authors.lastname: Brust
authors.forename: J
authors.initials: J
authors.lastname: Wober
authors.forename: R
authors.initials: R
authors.lastname: Syhre
authors.forename: H J
authors.initials: HJ
authors.lastname: Pietzsch
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D007650:Ketanserin / Q000737:chemistry / Q000378:metabolism; D008297:Male; D009942:Organometallic Compounds / Q000378:metabolism* / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism*; D012211:Rhenium / Q000378:metabolism* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D009942:Organometallic Compounds; D015609:Organotechnetium Compounds; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012211:Rhenium; D007650:Ketanserin