Synthesis and evaluation of pyrazolo[1,5-b]pyridazines as selective cyclin dependent kinase inhibitors

被引：28

作者：

Stevens, Kirk L. ^{[1
]}

Reno, Michael J. ^{[1
]}

Alberti, Jennifer B. ^{[1
]}

Price, Daniel J. ^{[2
]}

Kane-Carson, Laurie S. ^{[3
]}

Knick, Victoria B. ^{[4
]}

Shewchuk, Lisa M. ^{[2
]}

Hassell, Anne M. ^{[2
]}

Veal, James M. ^{[1
]}

Davis, Stephen T. ^{[4
]}

Griffin, Robert J. ^{[5
]}

Peel, Michael R. ^{[1
]}

机构：

[1] GlaxoSmithKline, Dept Oncol, Res Triangle Pk, NC 27709 USA

[2] GlaxoSmithKline, Dept Computat & Struct Chem, Res Triangle Pk, NC 27709 USA

[3] GlaxoSmithKline, Dept Mol Biochem, Res Triangle Pk, NC 27709 USA

[4] GlaxoSmithKline, Dept Canc Biol, Res Triangle Pk, NC 27709 USA

[5] GlaxoSmithKline, Dept Drug Metab & Pharmacokinet, Res Triangle Pk, NC 27709 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 21期

关键词：

Cyclin-dependant kinase inhibitor; CDK2; CDK4; VEGFR-2; GSK3; beta; Pyrazolo [1,5-b] pyridazine; Cancer;

D O I：

10.1016/j.bmcl.2008.09.069

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of pyrazolo[1,5-b]pyridazines have been synthesized and identified as cyclin dependant kinase inhibitors potentially useful for the treatment of solid tumors. Modi. cation of the hinge-binding amine or the C(2)- and C(6)- substitutions on the pyrazolopyridazine core provided potent inhibitors of CDK4 and demonstrated enzyme selectivity against VEGFR-2 and GSK3 beta. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：5758 / 5762

页数：5

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