In vitro aldose reductase inhibitory activity of 5-benzyl-2,4-thiazolidinediones.
Several 5-benzyl-2,4-thiazolidinediones (5-7) were synthesised and tested as in vitro aldose reductase (ALR2) inhibitors. Most of them, particularly N-unsubstituted 5-benzyl-2,4-thiazolidinediones 5 and (5-benzyl-2,4-dioxothiazolidin-3-yl)acetic acids 7, displayed moderate to high inhibitory activity levels. In detail, the insertion of an acetic chain on N-3 significantly enhanced ALR2 inhibitory potency, leading to acids 7 which proved to be the most effective among the tested compounds. In addition, in N-unsubstituted derivatives 5 the presence of an additional aromatic ring on the 5-benzyl moiety was generally beneficial. In fact, the ALR2 inhibition results of compounds 5-7, compared to those of the previously assayed corresponding 5-arylidene-2,4-thiazolidinediones, indicated that N-unsubstituted derivatives 5b, c and d, which bore an additional aromatic group in the para position of the 5-benzyl residue, were significantly more effective than their 5-arylidene counterparts; in all other cases, the saturation of the exocyclic double bond CC in 5 brought about a moderate decrease in activity.
Rakowitz
Dietmar
D
Institute of Pharmacy, University of Innsbruck, Innrain 52a, A-6020 Innsbruck, Austria.
Maccari
Rosanna
R
Ottanà
Rosaria
R
Vigorita
Maria Gabriella
MG
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D045162:Thiazolidinediones / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D045162:Thiazolidinediones; D000449:Aldehyde Reductase