Abstract
Baclofen (
1
) is a potent and selective agonist for bicuculline-insensitive GABA
B
receptors and is used clinically as an antispastic and muscle relaxant agent. In the search for new bioactive chemical entities that bind specifically to GABA
B
receptors, we report here the synthesis of certain baclofen homologues, namely (
R,S
)-5-amino-3-arylpentanoic acid hydrochlorides (
R,S
)-
1a
–
h
as well as (
R,S
)-5-amino-3-methylpentanoic acid [(
RS
)-
1i
] to be evaluated as GABA
B
R agonists. Compound
1a
is an agonist to GABA
B
receptors with an EC
50
value of 46 μM on tsA201 cells transfected with GABA
B1b
/GABA
B2
/Gqz5, being the most active congener among all the synthesized compounds.