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

被引：79

作者：

Cockcroft, XL ^{[1
]}

Dillon, KJ ^{[1
]}

Dixon, L ^{[1
]}

Drzewiecki, J ^{[1
]}

Kerrigan, F ^{[1
]}

Loh, VM ^{[1
]}

Martin, NMB ^{[1
]}

Menear, KA ^{[1
]}

Smith, GCM ^{[1
]}

机构：

[1] KuDOS Pharmaceut Ltd, Cambridge CB4 0WG, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 04期

关键词：

PARP-1; inhibitor; phthalazinone; DNA repair; anti-cancer; BRCA2-deficient cell;

D O I：

10.1016/j.bmcl.2005.10.081

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

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. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：1040 / 1044

页数：5

共 12 条

[11] Endothelial dysfunction in a rat model of endotoxic shock - Importance of the activation of poly(ADP-ribose) synthetase by peroxynitrite [J].