ACID-DERIVATIVES OF BENZISOTHIAZOLE-1,1-DIOXIDE AS INHIBITORS OF RAT LENS ALDOSE REDUCTASE

A number of 6-substituted 1,2-benzisothiazole-1,1-dioxide alkanoic aci ds were synthesized and evaluated for crude rat lens aldose reductase inhibitory activity. The inhibitory potency of the acetic (6a, 10a), p ropionic (6b, 10b, 11b), and isopropionic (6c, 10c, 11c) derivatives w as very similar and generally lower than that of the reference compoun d, Sorbinil. The presence of an acyl moiety on the amino group in posi tion 6, as in the acetic and propionic derivatives 14a-f and 15a,b, re spectively, resulted in a significant increase in activity. A good pot ency was shown by compounds 14g and 15g, in which a second carboxylic function is present on the 6-acylamino group. Also the open products 1 6, which contain the phenylsulfonyl fragment found in several known in hibitors of aldose reductase, were obtained and tested in the rat lens assay.