Isomers of substituted 3-benzo[b]furyl and 3-thienylaminobutyric acids as potent ligands of the GABA-B receptor: synthesis and preparative liquid chromatographic separation

Baclofen (4-amino-3-(4-chlorophenyl) butyric acid) is the only selective ag onist for GABA-B receptors. Its R-(-)-enantiomer is about 100 times more ac tive than the S(+)-enantiomer(1,2). In the search for new compounds that bi nd to GABA-B receptors, it is very important to clarify the structural requ irements. The authors report the synthesis and separation of isomers of var ious 3-heteroaromatic (benzo[b]furan and thiophen) aminobutyric acids. The 4 amino-3-(7-methylbenzo [b] furan-2-yl)butanoic acid is a potent and speci fic ligand for GABA-B receptors, with an IC50 value of 5.4 mu M for the dis placement of [H-3] GABA.