Phthalazinones. Part 1: The design and synthesis of a novel series of potent inhibitors of poly(ADP-ribose)polymerase

被引：89

作者：

Loh, VM

Cockcroft, XL

Dillon, KJ

Dixon, L

Drzewiecki, J

Everlsey, PJ

Gomez, S

Hoare, J

Kerrigan, F

Matthews, ITW

Menear, KA

Martin, NMB

Newton, RF

Paul, J

Smith, GCM

Vile, J

Whittle, AJ

机构：

[1] KuDOS Horsham Ltd, Horsham RH13 5PX, W Sussex, England

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

[3] Maybridge, Tintagel PL34 0HW, Cornwall, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 09期

关键词：

D O I：

10.1016/j.bmcl.2005.03.026

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Screening of the Maybridge compound collection identified 4-arylphthalazinones as micromolar inhibitors of PARP-1 catalytic activity. Subsequent optimisation of both inhibitory activity and metabolic stability led to a novel series of meta-substituted 4-benzyl-2H-phthalazin-1-ones with low nanomolar, cellular activity as PARP-1 inhibitors and promising metabolic stability in vitro. © 2005 Elsevier Ltd. All rights reserved.

引用

页码：2235 / 2238

页数：4

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