The synthesis of 1-(3,4-DICHLOROPHENYLACETYL)-2- [(3-FLUOROPYRROLIDINYL)METHYL]-PIPERIDlNE: a potential PET imaging agent for the kappa opiate receptor
The compound was synthesized as a fluorine labeled derivative of the Upjohn kappa specific ligand, U-50488. Two successful nucleophillic reaction schemes were reported. Results from the first scheme provided sufficient amounts of cold standards to: 1) perform in vitro binding studies; and 2) facilitate the identification of a radiolabeled final compound. The first scheme, however, fluorinated the compound early on in the synthesis and thus was unsuitable for the isolation of a radiolabeled version of the compound, due to the short half-life of [18 F]. Although, the product yield of the second reaction scheme was extremely low, the identification results have confirmed that the complete synthesis of an [18 F]-labeled kappa ligand is possible. F19- NMR data indicated that the compound exists as a pair of diastereoisomers. Separation of the isomers was achieved by HPLC methods. Results from the binding assay are still pending. If the results are positive, then the [18 F]-labeled compound will be further studied as a potential probe for imaging the opioid kappa receptor distributions of the brain in vivo, via positron emission tomography (PET).