N-(4-[~18F]-fluoropyridin-2-yl)-N-{2-[4-(2-methoxyphenyl) piperazin-l-yl]ethyl}carboxamides as analogs of WAY100635. New PET tracers of serotonin 5-HTia receptors

摘要

N-(4-[~18F]-Fluoropyridin-2-yl)-N-{2-[4-(2-methoxyphenyl)piperazin-l-yl]ethyl}-carboxamides were prepared by labeling their 4-nitropyridin-2-yl precursors through nitro substitution by the ~18F anion. In vitro and in vivo tests showed that the cyclohexanecarboxamide derivative is a reversible, selective and high affinity 5-HTia receptor antagonist (IC50 = 0.29 nM, k_i= 0.18 nM) with high brain uptake, slow brain clearance and stability to defluorination when compared with conventional standards. This PET radio-ligand is a promising candidate for an improved in vivo quantification of 5-HT_1A receptors in neuro-psychiatric disorders.