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Synthesis of novel WAY 100635 derivatives containing a norbornene group and radiofluorination of [ 18 F]AH1.MZ as a serotonin 5‐HT 1A receptor antagonist for molecular imaging

2009; Wiley; Volume: 52; Issue: 6 Linguagem: Inglês

10.1002/jlcr.1589

1099-1344

Matthias M. Herth, Vasko Kramer, Frank Rösch,

Fluorine in Organic Chemistry

Abstract 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. 18 F‐labelling via [ 18 F]FETos to [ 18 F]AH1.MZ was carried out in radiochemical yields of >70%. The final formulation of injectable solutions including [ 18 F]FETos synthon synthesis, radiosynthesis and semi‐preparative high‐performance liquid chromatography (HPLC) separation took no longer than 130 min and provided [ 18 F]AH1.MZ with a purity of >98% as indicated by analytical HPLC analyses. Copyright © 2009 John Wiley & Sons, Ltd.