☆ 4.5 Article

Structure-based design of imidazo[1,2-a] pyrazine derivatives as selective inhibitors of Aurora-A kinase in cells

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2010)

期刊

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷 20, 期 20, 页码 5988-5993

出版社

PERGAMON-ELSEVIER SCIENCE LTD

DOI: 10.1016/j.bmcl.2010.08.091

关键词

Aurora-A; Selectivity; Kinases

类别

Chemistry, Medicinal Chemistry, Organic

资金

NHS
Cancer Research UK [CUK] [C309/A8274]
Breakthrough Breast Cancer [AURA 05/06]

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摘要

Co-crystallisation of the imidazo[ 1,2-a] pyrazine derivative 15 (3-chloro-N-(4-morpholinophenyl)-6-( pyridin-3-yl)imidazo[1,2-a]pyrazin-8-amine) with Aurora-A provided an insight into the interactions of this class of compound with Aurora kinases. This led to the design and synthesis of potent Aurora-A inhibitors demonstrating up to 70-fold selectivity in cell-based Aurora kinase pharmacodynamic biomarker assays. (c) 2010 Elsevier Ltd. All rights reserved.

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