GABA(B) PHARMACOPHORIC PATTERN BASED ON CONFORMATIONAL-ANALYSIS OF 3-HETEROAROMATIC BACLOFEN ANALOGS

Substituting a furan, a thiophen, a benzo[b]furan or a benzo[b]thiophe n ring for the p-chlorophenyl moiety of baclofen has led to GABA(B) (G ABA = gamma-aminobutyric acid) ligands with different affinities accor ding to the nature of the heteroaromatic ring, and the nature and posi tion of its substituent. In order to determine the structural requirem ents that are important for GABA(B) affinity, we have aligned the 3D s tructures of several 3-heteroaromatic baclofen analogues with that of baclofen. As a result, we have suggested a pharmacophoric pattern for 3-heteroaromatic baclofen analogues. The 3D structures have been studi ed by X-ray diffraction and by ab initio molecular orbital calculation s.