The synthesis and SAR of 2-amino-pyrrolo[2,3-d]pyrimidines:: A new class of Aurora-A kinase inhibitors

被引：57

作者：

Moriarty, Kevin J. ^{[1
]}

Koblish, Holly K. ^{[1
]}

Garrabrant, Thomas ^{[1
]}

Maisuria, Jahanvi ^{[1
]}

Khalil, Ehab ^{[1
]}

Ali, Farah ^{[1
]}

Petrounia, Loanna P. ^{[1
]}

Crysler, Carl S. ^{[1
]}

Maroney, Anna C. ^{[1
]}

Johnson, Dana L. ^{[1
]}

Galemmo, Robert A., Jr. ^{[1
]}

机构：

[1] PRDUS LLC, Johson & Johnson, Spring House, PA 19477 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 22期

关键词：

Aurora-A; 2-amino-pyrrolo[2,3-d]pyrimidine; anti-proliferative; polyploidy;

D O I：

10.1016/j.bmcl.2006.08.080

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new class of Aurora-A inhibitors have been identified based on the 2-amino-pyrrolo[2,3-d]pyrimidine scaffold. Here, we describe the synthesis and SAR of this novel series. We report compounds which exhibit nanomolar activity in the Aurora-A biochemical assay and are able to inhibit tumor cell proliferation. This study culminates in compound 30, an inhibitor with potent activity against Aurora A (IC50 = 0-008 mu M), anti-proliferative activity against several tumor cell lines and induces polyploidy in H460 cells. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：5778 / 5783

页数：6

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