Synthesis and aldose reductase inhibitory activity of a new series of benz[h]cinnolinone derivatives.
Following our previous studies on pyridazinone carboxylic acids as potent and selective aldose reductase (ALR2) inhibitors, a new series of benzo[h]cinnolinone carboxylic acids, variously substituted at the positions 4, 7-10 and differently modified both at the central ring and at the acidic side chain, were synthesized and tested as inhibitors of ALR2. Comparison with previously synthesized compounds allows us to define more precisely structure-activity relationships for this class of compounds. In fact, in addition to the importance of the acidic side chain, their properties are highly influenced by the substituents present on the benzo[h]cinnolinone nucleous, with potency ranging from that of Sorbinil to very weakly active compounds.
Costantino
L
L
Dipartimento di Scienze Farmaceutiche, Modena, Italy.
Rastelli
G
G
Cignarella
G
G
Barlocco
D
D
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D007908:Lens, Crystalline / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology
D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D011724:Pyridazines; D000449:Aldehyde Reductase