Document Report Card

ID: ALA3421614

Journal: J Med Chem

Title: Identification of novel aldose reductase inhibitors based on carboxymethylated mercaptotriazinoindole scaffold.

Authors: Stefek M, Soltesova Prnova M, Majekova M, Rechlin C, Heine A, Klebe G.

Abstract: Fifteen compounds, sharing an indole-1-acetic acid moiety as a common fragment, were selected from commercial databases for testing aldose reductase inhibition. 3-Mercapto-5H-1,2,4-triazino[5,6-b]indole-5-acetic acid (13) was the most promising inhibitor, with an IC50 in the submicromolar range and high selectivity, relative to aldehyde reductase. The crystal structure of aldose reductase complexed with 13 revealed an interaction pattern explaining its high affinity. Physicochemical parameters underline the excellent "leadlikeness" of 13 as a promising candidate for further structure optimizations.

CiteXplore: 25695864

DOI: 10.1021/jm5015814