A New Synthesis Method and GABA Transporters Inhibitory Activities of Tiagabine and Its Analogues1

A new synthetic method and GABA transporter inhibitory activities of Tiagabine and its analogues are described. The key intermediates 4-tosyl-1,1-diaryl/heteroaryl-1-butene 10a-10e were synthesized by Wittig reaction, and followed by N-alkylation with (R)-3-piperidinecarboxylate. The resulting N-diheterocyclylalkenylpiperidine-3-carboxylic acid ester 11a-11e were saponified and then acidified to get the target compounds 1a-1e. The preliminary bioassays show that compound 1a-1e exhibited excellent inhibition of [3H]-GABA uptake in vitro of culture cells.