Aldose reductase inhibition by 2,4-oxo and thioxo derivatives of 1,2,3,4-tetrahydroquinazoline

Abstract Inhibitors of aldose reductase are believed to be useful for the treatment of diabetic complications. Original [(2,4-dioxo-1,2,3,4-tetrahydro)quinazolin-1-yl] acetic acids and their thioxo derivatives have been synthesized and examined for their ability to inhibit aldose reductase in vitro and in vivo . Most were active in vitro on rat lens aldose reductase in the 10 −7 molar range. Compound V 16 , which has a (2′-fluoro-4′-bromo)benzyl substituent on nitrogen N-3 was found in hypergalactosemic rats to be a good inhibitor of galactitol accumulation in sciatic nerves and to prevent cataract formation.