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[摘要]：In the search for an optimal fluorine-18-labeled positron emission tomography (PET) radiotracer for imaging metabotropic glutamate receptor subtype 5 (mGluRS), we have prepared a series of five alpha-fluorinated derivatives based on the ABP688 structural manifold by application of a two-step enolization/NFSI a-fluorination method. Their binding affinities were evaluated in vitro, and the most promising candidate (Z)-16 exhibited a K-i of 5.7 nM and a clogP value of 2.3. The synthesis of the precursor tosylate (E)-22 revealed a preference for the (E)-configurational isomer (K-i = 31.2 nM), and successful radiosynthesis afforded (E)-[F-18]-16 which was used as a model PET tracer to establish plasma and PBS stability. (E)-[F-18]-16 (K-d = 70 nM) exhibited excellent specificity for mGluRS in autoradiographic studies on horizontal rat brain slices in vitro. |
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