Synthesis and pharmacological evaluation of gamma-aminobutyric acid analogues. New ligand for GABAB sites.
Baclofen (beta-p-chlorophenyl-GABA) is the only selective agonist for the bicuculline-insensitive GABAB receptor. We report the synthesis of new GABA analogues and baclofen analogues. In vitro, two compounds, 4-amino-3-benzo[b]furan-2-ylbutanoic acid (9g) and 4-amino-3-(5-methoxybenzo[b]furan-2-yl)butanoic acid (9h), showed an affinity for the GABAB receptor. The results obtained with racemic compounds of benzofuran structure, new for this series, and the surprising inactivity of compound 3a (4-amino-3-(4-hydroxyphenyl)butanoic acid) permit the proposal of an hypothesis for the structure-activity relationships with regard to GABAB receptor.
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D018080:Receptors, GABA-B; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology
D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D001418:Baclofen