Phthalazinones 2: Optimisation and synthesis of novel potent inhibitors of poly(ADP-ribose)polymerase
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- 作者：Xiao-ling Cockcroft ; Krystyna J. Dillon ; Lesley Dixon ; Jan Drzewiecki ; Frank Kerrigan ; Vincent M. Loh ; Jr. ; Niall M.B. Martin ; Keith A. Menear and Graeme C.M. Smith
- 关键词：PARP-1 inhibitor ; Phthalazinone ; DNA repair ; Anti-cancer ; BRCA2-deficient cell
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2006
- 出版时间：15 February 2006
- 年：2006
- 卷：16
- 期：4
- 页码：1040-1044
- 全文大小：168 K
文摘
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.