Spiro-isoquinoline-pyrrolidines and analogs thereof useful as aldose reductase inhibitors

DETAILED DESCRIPTION We claim: 1.
The compounds of structural formula (I) ##STR5## wherein R.
sup.
1 and R.
sup.
2 are independently hydrogen, alkyl containining 1 to 6 carbon atoms, halogen, lower alkoxy containing 1 to 6 carbon atoms, trifluoromethyl, nitro, aryl or aryl(lower alkyl)oxy wherein aryl containing 6 to 10 carbon atoms and lower alkyl contains 1 to 6 carbon atoms; and R.
sup.
3 is hydrogen, alkyl containing 1 to 6 carbon atoms, lower alkoxy containing 1 to 6 carbon atoms, trifluoromethyl, nitro, aryl or aryl(lower alkyl)oxy wherein aryl contains 6 to 10 carbon atoms and lower alkyl contains 1 to 5 carbon atoms.
2.
The compounds according to claim 1 wherein R.
sup.
1 and R.
sup.
2 are independently hydrogen or halogen; and R.
sup.
3 is hydrogen, halogen or trifluoromethyl.
3.
The compound according to claim 2 2-[(2-benzothiazolylmethyl)spiro[isoquinoline-4(1H), 3'-pyrrolidine]-1,2',3,5'(2H)-tetrone.
4.
The compound according to claim 2 2-[(2-benzothiazolylmethyl)-6-fluorospiro[isoquinoline-4(1H), 3'-pyrrolidine]-1,2',3,5'(2H)-tetrone.
5.
The compound according to claim 2 2-[[5-(trifluoromethyl)-2-benzothiazolyl]methyl]spiro[isoquinoline-4-(1H), 3'-pyrrolidine]-1,2',3,5'(2H)-tetrone.
6.
The compound according to claim 2 6-fluoro-2-[[5-(trifluoromethyl)-2-benzothiazolyl]methyl]spiro[isoquinoline -4(1H), 3'-pyrrolidine]-1,2',3,5'(2H)-tetrone.
7.
A pharmaceutical composition for preventing or relieving neuropathy, nephropathy, retinopathy, or cataracts in a diabetic mammal, which comprises an effective amount of claim 1 and a pharmaceutically acceptable carrier.
8.
A method of preventing or relieving neuropathy, nephropathy, retinopathy, or cataracts in a diabetic mammal, which comprises administering to said mammal an alleviating or prophylactic amount of a compound of claim 1.




Description:
BACKGROUND OF THE INVENTION This invention relates to spiro-isoquinoline-pyrrolidines and their pharmaceutically acceptable salts thereof, to processes for their preparation, to methods for using the compounds, and to pharmaceutical preparations thereof