SYNTHESIS AND ALDOSE REDUCTASE INHIBITORY ACTIVITY OF NEW N-(BENZYLOXY) GLYCINE DERIVATIVES

This paper reports the synthesis and aldose reductase (AR) inhibitory properties of some N-(benzyloxy) glycine derivatives (compounds 2-6), structurally related to the previously described N-(aroyl)-N-(arylmeth yloxy) glycines A which had proved to possess an appreciable AR inhibi tory activity. In compounds 2-5, spacers of different lengths and degr ees of rigidity were inserted between the phenyl ring and the carbonyl group of type A derivatives; compound 6 differs from the most active type A derivative (compound 1) in the replacement of the methoxy moiet y in the para position of the benzoyl side-chain with a group with dif ferent electronic characteristics, such as the trifluoromethyl moiety. Biological results indicated that among compounds 2-5 only derivative 3, which presents a CH2CH2 spacer between the phenyl and the carbonyl moiety, proved to possess AR inhibitory properties analogous to those of 1, while all the other compounds proved to be devoid of any signif icant activity. Furthermore, compound 6 showed an inhibitory activity about 3 times lower than that of 1. (C) 1998 Elsevier Science S.A. All rights reserved.