Design, synthesis, and preliminary bioactivity evaluation of N-benzylpyrimidin-2-amine derivatives as novel histone deacetylase inhibitor

Chem Biol Drug Des. 2017 Nov;90(5):936-942. doi: 10.1111/cbdd.13019. Epub 2017 Jun 12.

Abstract

Histone deacetylase (HDAC) inhibitors have been identified for the treatment of cancer. Lately, we designed and synthesized a series of substituted N-benzylpyrimidin-2-amine derivatives as potent HDAC inhibitors. In vitro HDAC inhibitory activities and antiproliferative activities of target compounds were investigated. Some target compounds showed potent HDAC inhibitory activities and possessed obvious antiproliferative activity against tumor cells. Target compounds 6a, 6d, 8a, 8c, and 8f not only exhibited almost equally enzymatic inhibitory activity with SAHA, but showed better antiproliferative activities.

Keywords: anticancer; histone deacetylase; inhibitor; tumor.

MeSH terms

  • Amination
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Benzyl Compounds / chemical synthesis
  • Benzyl Compounds / chemistry
  • Benzyl Compounds / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Histone Deacetylase Inhibitors / chemical synthesis
  • Histone Deacetylase Inhibitors / chemistry*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / metabolism
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology*

Substances

  • Antineoplastic Agents
  • Benzyl Compounds
  • Histone Deacetylase Inhibitors
  • Pyrimidines
  • Histone Deacetylases