Synthesis and aldose reductase inhibitory activities of novel thienocinnolinone derivatives

A Pau; B Asproni; G Boatto; G E Grella; P De Caprariis; L Costantino; G A Pinna

doi:10.1016/j.ejps.2003.12.005

Synthesis and aldose reductase inhibitory activities of novel thienocinnolinone derivatives

Eur J Pharm Sci. 2004 Mar;21(4):545-52. doi: 10.1016/j.ejps.2003.12.005.

Authors

A Pau¹, B Asproni, G Boatto, G E Grella, P De Caprariis, L Costantino, G A Pinna

Affiliation

¹ Dipartimento Farmaco Chimico Tossicologico, Università di Sassari, Via Muroni 23/A, 07100 Sassari, Italy. pau@ssmain.uniss.it

PMID: 14998586
DOI: 10.1016/j.ejps.2003.12.005

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aldehyde Reductase / antagonists & inhibitors*
Aldehyde Reductase / metabolism
Animals
Carboxylic Acids / chemical synthesis*
Carboxylic Acids / pharmacology
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Swine
Thiophenes / chemical synthesis*
Thiophenes / pharmacology

Substances

Carboxylic Acids
Enzyme Inhibitors
Thiophenes
Aldehyde Reductase