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ID: ALA1134951

Journal: Bioorg Med Chem Lett

Title: Substituted uracil derivatives as potent inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1).

Authors: Steinhagen H, Gerisch M, Mittendorf J, Schlemmer KH, Albrecht B.

Abstract: A new class of PARP-1 inhibitors, namely substituted fused uracil derivatives were synthesised. Starting from a derivative with an IC(50)=2microM the chemical optimisation program led to compounds with more than a 100-fold increase in potency (IC(50)<20nM). Additionally, physicochemical and pharmacokinetic properties were evaluated. It could be shown that compounds bearing a piperazine or phenyl substituted betaAla-Gly side chain exhibited the best overall profile.

CiteXplore: 12372530

DOI: 10.1016/s0960-894x(02)00602-9