Synthesis and aldose reductase inhibitory activity of a new series of benzo[h]cinnolinone derivatives

Following our previous studies on pyridazinone carboxylic acids as potent a nd selective aldose reductase (ALR2) inhibitors, a new series of benzo[h]ci nnolinone carboxylic acids, variously substituted at the positions 4, 7-10 and differently modified both at the central ring and at the acidic side ch ain, were synthesized and tested as inhibitors of ALR2. Comparison with pre viously 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 influ enced by the substituents present on the benzo[h]cinnolinone nucleous, with potency ranging from that of Sorbinil to very weakly active compounds. (C) 2000 Elsevier Science S.A. All rights reserved.