Pharmaceutical compositions and methods of treating a glutamate abnormality and effecting a neuronal activity in an animal using NAALADase inhibitors

A method of treating a glutamate abnormality in an animal, comprising administering to said animal an effective amount compound of formula I:

• ##STR50## or a pharmaceutically acceptable salt or hydrate thereof, wherein:
• R.sub.1 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.9 straight or branched chain alkyl, C.sub.2 -C.sub.9 straight or branched chain alkenyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.5 -C.sub.7 cycloalkenyl and Ar, wherein said R.sub.1 is unsubstituted or substituted with carboxy, C.sub.3 -C.sub.8 cycloalkyl, C.sub.5 -C.sub.7 cycloalkenyl, halo, hydroxy, nitro, trifluoromethyl, C.sub.1 -C.sub.6 straight or branched chain alkyl, C.sub.2 -C.sub.6 straight or branched chain alkenyl, C.sub.1 -C.sub.9 alkoxy, C.sub.2 -C.sub.9 alkenyloxy, phenoxy, benzyloxy, amino, Ar or mixtures thereof;
• X is CR.sub.3 R.sub.4, O or NR.sub.1 ;
• R.sub.3 and R.sub.4 are independently selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 straight or branched chain alkyl, C.sub.2 -C.sub.6 straight or branched chain alkenyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.5 -C.sub.7 cycloalkenyl, Ar, halo and mixtures thereof;
• R.sub.2 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.9 straight or branched chain alkyl, C.sub.2 -C.sub.9 straight or branched chain alkenyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.5 -C.sub.7 cycloalkenyl and Ar, wherein said R.sub.2 is unsubstituted or substituted with carboxy, C.sub.3 -C.sub.8 cycloalkyl, C.sub.5 -C.sub.7 cycloalkenyl, halo, hydroxy, nitro, trifluoromethyl, C.sub.1 -C.sub.6 straight or branched chain alkyl, C.sub.2 -C.sub.6 straight or branched chain alkenyl, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 alkenyloxy, phenoxy, benzyloxy, amino, Ar or mixtures thereof;
• Ar is selected from the group consisting of 1-naphthyl, 2-naphthyl, 2-indolyl, 3-indolyl, 4-indolyl, 2-furyl, 3-furyl, tetrahydrofuranyl, tetrahydropyranyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, benzyl and phenyl, wherein said Ar is unsubstituted or substituted with halo, hydroxy, nitro, trifluoromethyl, C.sub.1 -C.sub.6 straight or branched chain alkyl, C.sub.2 -C.sub.6 straight or branched chain alkenyl, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 alkenyloxy, phenoxy, benzyloxy, amino or mixtures thereof.