Synthesis and aldose reductase inhibitory activities of novel thienocinnolinone derivatives.

A novel series of tetrahydrothieno[2,3-h]cinnolinone derivatives were synthesized and evaluated in vitro for their ability to inhibit aldose reductase (ALR2), an enzyme involved in the appearance of diabetic complications. Compounds 2e and 2j exert a remarkable inhibitory effect, with IC(50) of 7.6 and 18 microM, respectively. These compounds incorporate a valid pharmacophore for aldose reductase inhibitory activity represented by a thienocinnolinone template linked through a pentamethylene spacer to a carboxylic function.