title: Thienocinnolinone alkanoic acid derivatives as aldose reductase inhibitors.
abstract: A new series of 8-halogen-4,4a,5,6-tetrahydrothieno[2,3-h]cinnolinone-N2-alkanoic acids was prepared and tested for aldose reductase (ALR2) inhibitory activities. These compounds showed significant inhibitory activity against bovine lens ALR2, with the best compound 2e showing an IC(50) value of 31.4 microM. The presence of the C8-substituents here studied (Cl, Br) on the thienocinnolinone scaffold caused a decrease of the inhibitory potency by a factor of about 4 with respect to the unsubstituted parent compound, while the presence of a C8-methyl group, considered in a previous paper decreased the activity by a factor of about 2. Moreover, the length of the N2 alkanoic chain influences strongly the enzyme inhibitory activity. While most of the carboxylic acids ALR2 inhibitors are acetic acid derivatives, in the case of thienocinnolinone compounds, homologues higher than acetic acids showed to be more active.
authors.affiliation: Dipartimento Farmaco Chimico Tossicologico, Università di Sassari, Muroni 23/A, 07100 Sassari, Italy. pau@uniss.it
authors.forename: A
authors.initials: A
authors.lastname: Pau
authors.forename: B
authors.initials: B
authors.lastname: Asproni
authors.forename: G
authors.initials: G
authors.lastname: Murineddu
authors.forename: G
authors.initials: G
authors.lastname: Boatto
authors.forename: G E
authors.initials: GE
authors.lastname: Grella
authors.forename: D
authors.initials: D
authors.lastname: Rakowitz
authors.forename: L
authors.initials: L
authors.lastname: Costantino
authors.forename: G A
authors.initials: GA
authors.lastname: Pinna
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D013876:Thiophenes; D000449:Aldehyde Reductase