Synthesis of novel WAY 100635 derivatives containing a norbornene group and radiofluorination of [18F]AH1.MZ as a serotonin 5‐HT1A receptor antagonist for molecular imaging

5‐HT_1A receptors are involved in a variety of psychiatric disorders and in vivo molecular imaging of the 5‐HT_1A status represents an important approach to analyze and treat these disorders. We report herein the synthesis of three new fluoroethylated 5‐HT_1A ligands (AH1.MZ, AH2.MZ and AH3.MZ) as arylpiperazine derivatives containing a norbornene group. AH1.MZ (K_i= 4.2 nM) and AH2.MZ (K_i=30 nM) showed reasonable in vitro affinities to the 5‐HT_1A receptor, whereas AH3.MZ appeared to be non‐affine toward the 5‐HT_1A receptor. The receptor profile of AH1.MZ and AH2.MZ showed selectivity within the 5‐HT system. ¹⁸F‐labelling via ¹⁸F]FETos to ¹⁸F]AH1.MZ was carried out in radiochemical yields of >70%. The final formulation of injectable solutions including ¹⁸F]FETos synthon synthesis, radiosynthesis and semi‐preparative high‐performance liquid chromatography (HPLC) separation took no longer than 130 min and provided ¹⁸F]AH1.MZ with a purity of >98% as indicated by analytical HPLC analyses. Copyright © 2009 John Wiley & Sons, Ltd.