4-Substituted-3-hydroxy-3-pyrroline-2,5-dione inhibitors of glycolic acid oxidase

DETAILED DESCRIPTION About 70% of all renal calculi contain oxalate as the main component of the matrix.
In the majority of patients the condition is associated with a higher than average level of metabolically produced oxalate.
The major pathway for biosynthesis of oxalate can be represented as follows: ##STR6## Glyoxylate is the major immediate forerunner of oxalate.
An inhibitor of glycolate oxidase (G.
O.
) will inhibit both the conversion of glyoxylate to oxalate as well as the production of glyoxylate from glycolate.
By reducing oxalic acid levels in the urine with the compounds of this invention, the formation of oxalate calculi will be reduced or prevented.
Compounds of formula (I) are potent inhibitors of glycolate oxidase and thus are useful in restricting oxalate levels in the kidney and urine.
Further, they are useful in the treatment and prevention of renal disease due to calcium oxalate stone formation in the kidney and bladder.
They also may be useful in the treatment of the genetically inherited diseases termed Hyperoxaluria types I and II in which very high levels of metabolic oxalate are present.
Compounds of formula (I) have been unexpectedly found to block the contractions of guinea pig ileum induced by Slow Reacting Substance of Anaphylaxis (SRS-A).
They are ineffective against contractions caused by histamine, which demonstrates specificity against SRS-A.
SRS-A is considered a major mediator in human allergic asthma.
Thus the compounds of formula (I) are useful in the treatment of allergy, especially allergic asthma.
Compounds of formula (I) can be prepared according to the following general routes: ##STR7## wherein R and R'--(CH.
sub.
2).
sub.
n -- represent substituents at the 4-position of the 3-hydroxy-3-pyrroline-2,5-dione in formula (I) above.
Route 1 is applicable when p in formula (I) above is 0.
Route 2 is applicable when Y in formula (I) above is (CH.
sub.
2).
sub.
m --O or (CH.
sub.
2).
sub.
m --S.
Route 3 is the most generally applicable and is the preferred route in the case when Y in formula (I) above is (CH