ISOMERIC BENZOYLPYRROLEACETIC ACIDS - SOME STRUCTURAL ASPECTS FOR ALDOSE REDUCTASE INHIBITORY AND ANTIINFLAMMATORY ACTIVITIES

A number of isomeric benzoylpyrroleacetic acids (1-6) were prepared an d tested in vitro for rat lenses aldose reductase activity. These pyrr ole derivatives are structurally related to the acidic nonsteroidal an tiinflammatory drugs. Therefore, their anti-inflammatory properties we re also evaluated in the carrageenan-induced rat paw edema model. Inhi bition of the aldose reductase enzyme was found to depend on the prese nce of both the benzoyl and acetic acid functionalities. Better activi ty resulted when these moieties were introduced at positions 1 and 3 o f the pyrrole ring. However, for anti-inflammatory activity, the aceti c acid group was not necessary and, in some cases, its presence result ed in a loss of activity. 3-Benzoylpyrrole-1-acetic acid (6) exhibited an IC50 of 2.5 mu M in the aldose reductase assay which is comparable to that of alrestatin (1.5 mu M). Compound 6, however, showed no anti -inflammatory activity at doses up to a 100 mg/kg, ip, in the rat paw model.