Synthesis and GCP II inhibitory activity of 4[4-(3-bromobenzyl)-5-hydroxyisoxazol-3-yl]benzoic acid heterocyclic analogs

A method for the synthesis of analogs of glutamate carboxypeptidase II inhibitor 4-[4-(3-bromobenzyl)-5-hydroxyisoxazol-3-yl]benzoic acid-4-[4-(3-bromobenzyl-5-hydroxypyrazol-3-yl]-benzoic acid and 4-[4-(3-bromobenzyl)-3-hydroxyisoxazol-5-yl]benzoic acid from 4-(2-ethoxycarbonylacetyl)benzoic acid was developed. The GCP II inhibitory activity of all the compounds synthesized was determined. Substitution of the 5-hydroxyisoxazole group by the 5-hydroxypyrazole group led toa complete loss of activity, while replacement with the 3-hydroxyylisoxazole gave the compound with slightly less inhibitoer activity comparing with the initial compound.