3-Thienyl- and 3-furylaminobutyric acids. Synthesis and binding GABAB receptor studies.
Baclofen (beta-(p-chlorophenyl)-GABA) is a selective agonist for the bicuculline-insensitive GABAB receptor. The search for new compounds that bind to the GABAB receptor is very important to clarify structural requirements. We report herein the synthesis and the binding studies of variously substituted 3-thienyl- and 3-furylaminobutyric acids. 4-Amino-3-(5-methyl-2-thienyl)butyric acid (5d) and 4-amino-3-(5-chloro-2-thienyl)butyric acid (5h) are potent and specific ligands for GABAB receptor. The IC50 values for the displacement of (R)-(-)-[3H]baclofen are 1.34 and 0.61 microM for 5d and 5h, respectively, as compared to 0.33 microM for baclofen.
Berthelot
P
P
Laboratoire de Pharmacie Chimique, Faculté de Pharmacie, Lille, France.
Vaccher
C
C
Flouquet
N
N
Debaert
M
M
Luyckx
M
M
Brunet
C
C
D000818:Animals; D001418:Baclofen / Q000378:metabolism; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D005663:Furans / Q000138:chemical synthesis* / Q000378:metabolism; D015394:Molecular Structure; D009118:Muscimol / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism; D013876:Thiophenes / Q000138:chemical synthesis* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism
D005663:Furans; D011963:Receptors, GABA-A; D013876:Thiophenes; C070483:4-amino-3-(5-methyl-2-thienyl)butyric acid; C070484:4-amino-3-(5-chloro-2-thienyl)butyric acid; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001418:Baclofen