Design and synthesis of novel pyrimidine hydroxamic acid inhibitors of histone deacetylases
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- 作者：Alastair D.G. Donald ; Vanessa L. Clark ; Sanjay Patel ; Francesca A. Day ; Martin G. Rowl ; s ; Judata Wibata ; Lindsay Stimson ; Anthea Hardcastle ; Sue A. Eccles ; Deborah McNamara ; Lindsey A. Needham ; Floren
- 关键词：HDAC ; Cancer ; Optimisation
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2010
- 出版时间：15 November 2010
- 年：2010
- 卷：20
- 期：22
- 页码：6657-6660
- 全文大小：291 K
文摘
Inhibition of histone deacetylase activity represents a promising new modality in the treatment of a number of cancers. A novel HDAC series demonstrating inhibitory activity in cell proliferation assays is described. Optimisation based on the introduction of basic amine linkers to effect good drug distribution to tumour led to the identification of a compound with oral activity in a human colon cancer xenograft study associated with increased histone H3 acetylation in tumour tissue.