Design and synthesis of novel pyrimidine hydroxamic acid inhibitors of histone deacetylases

作者：Donald Alastair D G^*; Clark Vanessa L; Patel Sanjay; Day Francesca A; Rowlands Martin G; Wibata Judata; Stimson Lindsay; Hardcastle Anthea; Eccles Sue A; McNamara Deborah; Needham Lindsey A; Raynaud Florence I; Aherne Wynne; Moffat David F

来源：Bioorganic & Medicinal Chemistry Letters, 2010, 20(22): 6657-6660.

DOI：10.1016/j.bmcl.2010.09.016

• HDAC
• Cancer
• Optimisation

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.

• 出版日期2010-11-15