Cockcroft Xiao-Ling, Dillon Krystyna J, Dixon Lesley, Drzewiecki Jan, Kerrigan Frank, Loh Vincent M, Martin Niall M B, Menear Keith A, Smith Graeme C M
KuDOS Pharmaceuticals Ltd 327 Cambridge Science Park, Milton Road, Cambridge, CB4 0WG, UK.
Bioorg Med Chem Lett. 2006 Feb 15;16(4):1040-4. doi: 10.1016/j.bmcl.2005.10.081. Epub 2005 Nov 15.
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.
我们之前曾描述过基于酞嗪酮支架发现聚（ADP - 核糖）聚合酶 -1（PARP -1）抑制剂的过程。随后对抑制活性、代谢稳定性和药代动力学参数进行的优化，产生了一系列新型的间位取代4 - 苄基 -2H - 酞嗪 -1 - 酮PARP -1抑制剂，这些抑制剂保持了低纳摩尔级别的细胞活性，在体内显示出良好的稳定性，并在细胞模型中具有疗效。
