Diphenylmethylene hydroxamic acids as selective class IIa histone deacetylase inhibitors

Bioorg Med Chem Lett. 2009 Oct 1;19(19):5684-8. doi: 10.1016/j.bmcl.2009.08.010. Epub 2009 Aug 7.

Abstract

We have identified a series of diphenylmethylene hydroxamic acids as novel and selective HDAC class IIa inhibitors. The original hit, N-hydroxy-2,2-diphenylacetamide (6), has sub-micromolar class IIa HDAC inhibitory activity, while the rigidified oxygen analogue, N-hydroxy-9H-xanthene-9-carboxamide (13), is slightly more selective for HDAC7 with an IC(50) of 0.05muM. Substitution of 6 allows for the modulation of selectivity and potency amongst the class IIa HDAC isotypes.

MeSH terms

  • Cell Line
  • Diphenylacetic Acids / chemical synthesis
  • Diphenylacetic Acids / chemistry*
  • Diphenylacetic Acids / pharmacology
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Histone Deacetylases / metabolism
  • Humans
  • Hydroxamic Acids / chemical synthesis
  • Hydroxamic Acids / chemistry*
  • Hydroxamic Acids / pharmacology
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / metabolism
  • Structure-Activity Relationship
  • Xanthenes / chemical synthesis
  • Xanthenes / chemistry*
  • Xanthenes / pharmacology

Substances

  • Diphenylacetic Acids
  • Enzyme Inhibitors
  • Hydroxamic Acids
  • N-hydroxy-2,2-diphenylacetamide
  • N-hydroxy-9H-xanthene-9-carboxamide
  • Protein Isoforms
  • Xanthenes
  • Histone Deacetylases