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

Bioorg Med Chem Lett. 2010 Nov 15;20(22):6657-60. doi: 10.1016/j.bmcl.2010.09.016. Epub 2010 Sep 21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Drug Design*
  • Histone Deacetylase Inhibitors / chemical synthesis*
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology
  • Humans
  • Hydroxamic Acids / chemical synthesis*
  • Hydroxamic Acids / chemistry
  • Hydroxamic Acids / pharmacology
  • Pyrimidines / chemistry*
  • Transplantation, Heterologous

Substances

  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Pyrimidines
  • pyrimidine