New Fluorinated Dopamine D2 Ligands with Benzofuran Skeleton. The Synthesis and in Vitro Evaluation

Abstract

New fluorinated ligands with N-[(1-ethyl-2-pyrrolidinyl)methyl]-2, 3-dihydrobenzofuran-7-carboxamide skeleton, which are useful as a prototype to develop ¹⁸F labelled in vivo radiotracer for positron emission tomography (PET), were synthesized, and their binding affinities for the dopamine D2 receptors were investigated. Fluorine atom was introduced at C-4 of the pyrrolidine ring (10) or at ethyl substituent at C-5 of the dihydrobenzofuran moiety (20). The in vitro IC₅₀ values of these ligands for the dopamine D2 receptors which were determined by their ability to inhibit the binding of [³H]spiperone binding in rat striatal membrane were 17 and 36 nM, respectively. Thus, the fluorinated compounds 10 and 20 may be possible candidates for further in vivo investigation.