title: Synthesis and aldose reductase inhibitory activity of triazine derivatives possessing acetic acid group.
abstract: N-Acetic acid derivatives of 6-aryl-pyrazolo-triazin-4-ones were synthesized for evaluation as new aldose reductase inhibitors. The intrinsic activity of each compound was assessed by measuring the inhibition of enzymatic activity in an isolated pig lens enzyme preparation. All the prepared compounds exhibited a significant in vitro aldose reductase inhibitory effect (10(-6) M less than or equal to IC50 less than or equal to 10(-4) M). Furthermore, biological activity (log 1/IC50) for most of the data sets could be correlated directly to electronic and steric parameters. Finally, spatial configuration of the most active derivative 6c (IC50 = 2 x 10(-6) M) was compared with that of tolrestat and with pharmacophor requirements of the aldose reductase inhibitor site using a molecular modeling system.
authors.affiliation: Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie, Université de Clermont-Ferrand I, France.
authors.forename: S
authors.initials: S
authors.lastname: Mavel
authors.forename: P
authors.initials: P
authors.lastname: Coudert
authors.forename: E
authors.initials: E
authors.lastname: Albuisson
authors.forename: E
authors.initials: E
authors.lastname: Duroux
authors.forename: P
authors.initials: P
authors.lastname: Bastide
authors.forename: J
authors.initials: J
authors.lastname: Couquelet
authors.forename: P
authors.initials: P
authors.lastname: Tronche
authors.forename: C
authors.initials: C
authors.lastname: Rubat
mesh_terms: D000085:Acetates / Q000737:chemistry*; D019342:Acetic Acid; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000085:Acetates; D011720:Pyrazoles; D014227:Triazines; D000449:Aldehyde Reductase; D019342:Acetic Acid