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.
Dipartimento Farmaco Chimico Tossicologico, Università di Sassari, Via Muroni 23/A, 07100 Sassari, Italy. pau@ssmain.uniss.it
A
A
Pau
B
B
Asproni
G
G
Boatto
G E
GE
Grella
P
P
De Caprariis
L
L
Costantino
G A
GA
Pinna
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013552:Swine; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology
D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D013876:Thiophenes; D000449:Aldehyde Reductase