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

H Steinhagen, M Gerisch, J Mittendorf…

Index: Steinhagen, Henning; Gerisch, Michael; Mittendorf, Joachim; Schlemmer, Karl-Heinz; Albrecht, Barbara Bioorganic and Medicinal Chemistry Letters, 2002 , vol. 12, # 21 p. 3187 - 3190

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Citation Number: 27

Abstract

A new class of PARP-1 inhibitors, namely substituted fused uracil derivatives were synthesised. Starting from a derivative with an IC50= 2μM the chemical optimisation program led to compounds with more than a 100-fold increase in potency (IC50< 20nM). Additionally, physicochemical and pharmacokinetic properties were evaluated. It could be shown that compounds bearing a piperazine or phenyl substituted βAla-Gly side chain ...