Synthesis and aldose reductase inhibitory activity of pyridazine derivatives possessing acetic acid group.
N-acetic acid and S-acetic acid derivatives of 5-arylidene pyridazines were synthesized for evaluation as new aldose reductase inhibitors. Intrinsic activity for each compound was assessed by measuring inhibition of enzymatic activity in an isolated pig lens enzyme preparation. All prepared compounds exhibited a significant in vitro aldose reductase inhibitory effect (10(-5) M less than or equal IC50 less than or equal to 10(-4) M). It was found that lipophilicity was important in increasing activity. Furthermore, this activity (log 1/IC50) could be correlated directly to a lipophilic parameter (log kw) for the whole data set.
Coudert
P
P
Groupe de Recherches en Pharmacochimie, Université de Clermont-Ferrand, France.
Rubat
C
C
Duroux
E
E
Bastide
P
P
Couquelet
J D
JD
Tronche
P
P
Albuisson
E
E
D000085:Acetates / Q000494:pharmacology; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007908:Lens, Crystalline / Q000201:enzymology; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology; D013552:Swine
D000085:Acetates; D011724:Pyridazines; D000449:Aldehyde Reductase