Phthalazinones 2: Optimisation and synthesis of novel potent inhibitors of poly (ADP-ribose) polymerase

X Cockcroft, KJ Dillon, L Dixon, J Drzewiecki…

文献索引：Cockcroft, Xiao-Ling; Dillon, Krystyna J.; Dixon, Lesley; Drzewiecki, Jan; Kerrigan, Frank; Loh Jr., Vincent M.; Martin, Niall M.B.; Menear, Keith A.; Smith, Graeme C.M. Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 4 p. 1040 - 1044

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被引用次数: 98

摘要

We have previously described the discovery of poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors based on a phthalazinone scaffold. Subsequent optimisation of inhibitory activity, metabolic stability and pharmacokinetic parameters has led to a novel series of meta- substituted 4-benzyl-2H-phthalazin-1-one PARP-1 inhibitors which retain low nM cellular activity and show good stability in vivo and efficacy in cell based models.