[Synthesis and evaluation of the aldose reductase inhibitory activity of new diaryl pyridazine-3-ones].
It has been possible to prepare from 4,6-diaryl pyridazinones a series of derivatives substituted in the 2-position by chains of various lengths bearing a carboxylic acid function. Pig lens aldose reductase inhibitory activity was evaluated for all compounds. N-acetic acid derivative 3c with a chlorine atom on the phenyl nucleus at the 6-position on the pyridazin ring was the most active pyridazinone with an IC50 value of 1.2 x 10(-5) M. Furthermore, it has been shown that lipophilicity and spatial configuration of the synthesized compounds took a prominent part on enzymatic activity.
Coudert
P
P
Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie, Clermond-Ferrand, France.
Duroux
E
E
Bastide
P
P
Couquelet
J
J
Tronche
P
P
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000201:enzymology; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine
D011724:Pyridazines; D000449:Aldehyde Reductase
Synthèse et évaluation de l'activité inhibitrice d'aldose réductase de nouvelles diaryl pyridazin-3-ones.