3-BENZO[B]FURYLAMINOBUTYRIC AND 3-BENZO[B]THIENYLAMINOBUTYRIC ACIDS AS GABA(B) LIGANDS - SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIP STUDIES

Baclofen (beta-p-chlorophenyl GABA) is one of the selective agonists f or the bicuculline-insensitive GABA(B) receptors. In the search for ne w compounds that bind to GABA(B) receptors it is very important to cla rify the structural requirements. We report the syntheses of and bindi ng studies on various S-heteroaromatic (benzo[b]furan and benzo[b]thio phen)aminobutyric acids. The 4-amino-3-(7-methyl-benzo[b]furan-2-yl)bu tanoic acid 8g is a potent and specific ligand for GABA(B) receptors, with an IC50 value of 5.4 mu M in the displacement of [H-3]GABA.