Identification of aminoethyl pyrrolo dihydroisoquinolinones as novel poly(ADP-ribose) polymerase-1 inhibitors

被引：17

作者：

Branca, Danila ^{[1
]}

Cerretani, Mauro ^{[1
]}

Jones, Philip ^{[1
]}

Koch, Uwe ^{[1
]}

Orvieto, Federica ^{[1
]}

Palumbi, Maria Cecilia ^{[1
]}

Rowley, Michael ^{[1
]}

Toniatti, Carlo ^{[1
]}

Muraglia, Ester ^{[1
]}

机构：

[1] IRBM, Merck Res Labs, I-00040 Rome, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 15期

关键词：

Parp1; Inhibitor; Anticancer; Indoles;

D O I：

10.1016/j.bmcl.2009.06.031

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

PARP inhibitors have been demonstrated to retard intracellular DNA repair and therefore sensitize tumor cells to cytotoxic agents or ionizing radiation. We report the identification of a novel class of PARP1 inhibitors, containing a pyrrolo moiety fused to a dihydroisoquinolinone, derived from virtual screening of the proprietary collection. SAR exploration around the nitrogen of the aminoethyl appendage chain of 1 led to compounds that displayed low nanomolar activity in a PARP1 enzymatic assay. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：4042 / 4045

页数：4

共 20 条

[1] HYDROGEN-PEROXIDE INSULT IN CULTURED MAMMALIAN-CELLS - RELATIONSHIPS BETWEEN DNA SINGLE-STRAND BREAKAGE, POLY(ADP-RIBOSE) METABOLISM AND CELL KILLING [J].