title: N-(4-[(18)F]-fluoropyridin-2-yl)-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}carboxamides as analogs of WAY100635. New PET tracers of serotonin 5-HT(1A) receptors.
abstract: N-(4-[(18)F]-Fluoropyridin-2-yl)-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-carboxamides were prepared by labeling their 4-nitropyridin-2-yl precursors through nitro substitution by the (18)F anion. In vitro and in vivo tests showed that the cyclohexanecarboxamide derivative is a reversible, selective and high affinity 5-HT1A receptor antagonist (IC50 = 0.29 nM, ki = 0.18 nM) with high brain uptake, slow brain clearance and stability to defluorination when compared with conventional standards. This PET radioligand is a promising candidate for an improved in vivo quantification of 5-HT1A receptors in neuropsychiatric disorders.
authors.affiliation: Departamento de Química Orgánica, Universidad de Alcalá, Alcalá de Henares, Madrid 28871, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: García
authors.affiliation: Departamento de Química Orgánica, Universidad de Alcalá, Alcalá de Henares, Madrid 28871, Spain.
authors.forename: Valentina
authors.initials: V
authors.lastname: Abet
authors.affiliation: Departamento de Química Orgánica, Universidad de Alcalá, Alcalá de Henares, Madrid 28871, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Alajarín
authors.affiliation: Departamento de Química Orgánica, Universidad de Alcalá, Alcalá de Henares, Madrid 28871, Spain. Electronic address: julio.alvarez@uah.es.
authors.forename: Julio
authors.initials: J
authors.lastname: Álvarez-Builla
authors.affiliation: CAI Cartografía Cerebral, Instituto Pluridisciplinar UCM, Paseo Juan XXIII, 1, Madrid 28040, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Delgado
authors.affiliation: CAI Cartografía Cerebral, Instituto Pluridisciplinar UCM, Paseo Juan XXIII, 1, Madrid 28040, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: García-García
authors.affiliation: CAI Cartografía Cerebral, Instituto Pluridisciplinar UCM, Paseo Juan XXIII, 1, Madrid 28040, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Bascuñana-Almarcha
authors.affiliation: Instituto Tecnológico PET, Calle Manuel Bartolomé Cossío 10, Madrid 28040, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Peña-Salcedo
authors.affiliation: Instituto Tecnológico PET, Calle Manuel Bartolomé Cossío 10, Madrid 28040, Spain.
authors.forename: James
authors.initials: J
authors.lastname: Kelly
authors.affiliation: CAI Cartografía Cerebral, Instituto Pluridisciplinar UCM, Paseo Juan XXIII, 1, Madrid 28040, Spain; Instituto Tecnológico PET, Calle Manuel Bartolomé Cossío 10, Madrid 28040, Spain. Electronic address: pozo@med.ucm.es.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Pozo
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D005462:Fluorine Radioisotopes; D008297:Male; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D011849:Radioactive Tracers; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*
chemical_list: D005462:Fluorine Radioisotopes; D010879:Piperazines; D011725:Pyridines; D011849:Radioactive Tracers; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
keywords: 5-HT(1A); Fluorine-18; N-(4-[(18)F]-fluoropyridin-2-yl)-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}carboxamides; Positron emission tomography; Radioligand