- Aldose reductase inhibition by 2,4-oxo and thioxo derivatives of 1,2,3,4-tetrahydroquinazoline
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Inhibitors of aldose reductase are believed to be useful for the treatment of diabetic complications.Original 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 V16, 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 andto prevent cataract formation.
- Billon, Florence,Delchambre, Chantal,Cloarec, Alix,Sartori, Eric,Teulon, Jean-Marie
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p. 121 - 126
(2007/10/02)
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- Quinazoline derivatives, compositions thereof and their use in treating diabetic complications
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The invention relates to compounds of the formula: STR1 in which R1 and R2 are each hydrogen, halogen, lower alkoxy or halo(lower)alkyl, R3 is dihalophenyl, naphthyl(lower)alkyl, phenyl(lower)alkyl substituted by one or two substituent(s) selected from the group consisting of halogen, lower alkoxy, halo(lower)alkyl and lower alkyl, or thienyl(lower)alkyl, R4 is carboxy or protected carboxy, Y is carbonyl, thiocarbonyl or sulfonyl and Z is lower alkylene, and pharmaceutically acceptable salts thereof, useful in the treatment of diabetic complications.
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