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.
Ansar
M
M
Laboratoire de Chimie Organique et Bioorganique, Faculté des Sciences Universitaires Chouaib Doukkali, El Jadida, Maroc.
Ebrik
S
S
Mouhoub
R
R
Vaccher
C
C
Vaccher
M P
MP
Flouquet
N
N
Bakkas
S
S
Taoufik
J
J
Debaert
M
M
Caignard
D H
DH
Renard
P
P
Berthelot
P
P
D000613:Aminobutyrates / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D015195:Drug Design; D018755:GABA Agonists / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D018756:GABA Antagonists / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D015394:Molecular Structure; D009118:Muscimol / Q000378:metabolism / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000187:drug effects; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000613:Aminobutyrates; D018755:GABA Agonists; D018756:GABA Antagonists; D008024:Ligands; D009419:Nerve Tissue Proteins; D018080:Receptors, GABA-B; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001418:Baclofen