title: Acid derivatives of benzisothiazole-1,1-dioxide as inhibitors of rat lens aldose reductase.
abstract: A number of 6-substituted 1, 2-benzisothiazole-1, 1-dioxide alkanoic acids were synthesized and evaluated for crude rat lens aldose reductase inhibitory activity. The inhibitory potency of the acetic (6a, 10a), propionic (6b, 10b, 11b), and isopropionic (6c, 10c, 11c) derivatives was very similar and generally lower than that of the reference compound, Sorbinil. The presence of an acyl moiety on the amino group in position 6, as in the acetic and propionic derivatives 14a-f and 15a, b, respectively, resulted in a significant increase in activity. A good potency was shown by compounds 14g and 15g, in which a second carboxylic function is present on the 6-acylamino group. Also the open products 16, which contain the phenylsulfonyl fragment found in several known inhibitors of aldose reductase, were obtained and tested in the rat lens assay.
authors.affiliation: Dipartimento di Scienze Farmaceutiche dell'Università di Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Da Settimo
authors.forename: G
authors.initials: G
authors.lastname: Primofiore
authors.forename: C
authors.initials: C
authors.lastname: La Motta
authors.forename: F
authors.initials: F
authors.lastname: Da Settimo
authors.forename: F
authors.initials: F
authors.lastname: Simorini
authors.forename: E
authors.initials: E
authors.lastname: Boldrini
authors.forename: P
authors.initials: P
authors.lastname: Bianchini
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D013844:Thiazoles; D000449:Aldehyde Reductase