A novel HDAC inhibitor with a hydroxy-pyrimidine scaffold

Bioorg Med Chem Lett. 2011 Jul 15;21(14):4164-9. doi: 10.1016/j.bmcl.2011.05.098. Epub 2011 Jun 2.

Abstract

Histone deacetylases (HDACs) are enzymes involved in many important biological functions. They have been linked to a variety of cancers, psychiatric disorders, and other diseases. Since small molecules can serve as probes to study the relevant biological roles of HDACs, novel scaffolds are necessary to develop more efficient, selective drug candidates. Screening libraries of molecules may yield structurally diverse probes that bind these enzymes and modulate their functions in cells. Here we report a small molecule with a novel hydroxy-pyrimidine scaffold that inhibits multiple HDAC enzymes and modulates acetylation levels in cells. Analogs were synthesized in an effort to evaluate structure-activity relationships.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Histone Deacetylase Inhibitors / chemical synthesis
  • Histone Deacetylase Inhibitors / chemistry*
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylases / chemistry*
  • Histone Deacetylases / metabolism
  • Humans
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology
  • Structure-Activity Relationship

Substances

  • Histone Deacetylase Inhibitors
  • Pyrimidines
  • Histone Deacetylases
  • pyrimidine