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-(arylmethyloxy) glycines A which had proved to possess an appreciable AR inhibitory activity. In compounds 2-5, spacers of different lengths and degrees 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 moiety in the para position of the benzoyl side-chain with a group with different 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 the possess AR inhibitory properties analogous to those of 1, while all the other compounds proved to be devoid of any significant activity. Furthermore, compound 6 showed an inhibitory activity about 3 times lower than that of 1.
Macchia
M
M
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Italy.
Barontini
S
S
Martinelli
A
A
Menchini
E
E
Nencetti
S
S
Orlandini
E
E
Romagnoli
F
F
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D000449:Aldehyde Reductase; D005998:Glycine