Potential GABA_b receptor antagonists. III. Folded baclofen analogues based on phthalide

Possible analogues of baclofen, 3-aminomethyl-5-chloro-, 3-aminomethyl-6-chloro- and 3-aminomethyl-5, 6-dichloro-isobenzofuran-1(3H)-one, have been prepared for evaluation as antispasticity agents. The corresponding 3-hydroxyisobenzofuran-1(3H)-one was reacted with ethyl acetoacetate under acidic conditions, and the keto ester hydrolysed and decarboxylated to give the 3-(2-oxopropyl)isobenzofuran-1(3H)-one; this was treated with hydrazoic acid, and the productwas hydrolysed. A parallel series of (3-oxo-1, 3-dihydroisobenzofuran-1-yl)glycines was obtained by treating the keto ester first with hydrazoic acid, and hydrolysis of the resulting acetamides.