Selective irreversible inhibitors of aldose reductase.
A series of 5-substituted-1,3-dioxo-1H-benz[de]isoquinoline-2(3H)-acetic acid analogues have been examined as irreversible inhibitors of aldose reductase. The 5-alpha-bromoacetamide and 5-alpha-iodoacetamide analogues 5 and 6 gave irreversible inhibition of aldose reductase while the 5-alpha-chloroacetamide analogue 3 did not show this type of inhibition. Protection studies indicate that irreversible inhibitions are occurring at the inhibitor binding site. Comparative irreversible inhibition studies with rat lens aldose reductase (RLAR) and rat kidney aldehyde reductase (RKALR) indicate that 5-alpha-haloacetamide analogues 5 and 6 are much more effective inhibitors of RLAR.
Smar
M W
MW
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Ohio State University, Columbus 43210.
Ares
J J
JJ
Nakayama
T
T
Itabe
H
H
Kador
P F
PF
Miller
D D
DD
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D000449:Aldehyde Reductase