Design, synthesis, and biological evaluation of the N-diarylalkenyl-piperidinecarboxylic acid derivatives as GABA uptake inhibitors (I)

Twenty novel N-diarylalkenyl-piperidinecarboxylic acid derivatives were synthesized and evaluated as γ-aminobutyric acid uptake inhibitors. The biological assay showed that (R)-1-[4,4-bis(3-phenoxymethyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic hydrochloride (4e) possessed almost as strong GAT1 inhibitory activity as tiagabine. The synthesis and structure–activity relationships are discussed.