Synthesis of novel phenylacetic acid derivatives with halogenated benzyl subunit and evaluation as aldose reductase inhibitors

In the course of our ongoing studies several substituted benzyloxyphenylacetic acids were prepared. Comparison of their aldose reductase inhibition with the biological activity obtained for recently evaluated benzoic acid analogues revealed the critical role of a methylene spacer between the aromatic core and the acidic function. Starting from the most potent derivative (i.e. 5d, IC50 = 20.9 μM) further structural modifications were performed and their influence on the inhibitory effect was established.