Synthesis of new N-substituted pyrrolidin-2-ones as cyclic analog of gamma-aminobutyric acid.

Some new N-substituted pyrrolidin-2-ones, cyclic analogs of baclofen and of 3-(5-methylbenzo[b]furan-2-yl)-gamma-aminobutyric acid, have been prepared starting from corresponding pyrrolidinones and characterized.

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 agonist for GABA-B receptors. Its R-(-)-enantiomer is about 100 times more active than the S-(+)-enantiomer. In the search for new compounds that bind to GABA-B receptors, it is very important to clarify the structural requirements. The authors report the synthesis and separation of isomers of various 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 specific ligand for GABA-B receptors, with an IC50 value of 5.4 microM for the displacement of [3H] GABA.