Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1379277 | Bioorganic & Medicinal Chemistry Letters | 2006 | 5 Pages |
Abstract
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.
Graphical abstractThe discovery of novel and cellularly potent PARP-1 inhibitors is described. Compound 36 is effective in specific killing of BRCA2-deficient tumour cells.Figure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Xiao-ling Cockcroft, Krystyna J. Dillon, Lesley Dixon, Jan Drzewiecki, Frank Kerrigan, Vincent M. Loh Jr., Niall M.B. Martin, Keith A. Menear, Graeme C.M. Smith,