Studies of the metabolic stability in cells of 5-(trifluoroacetyl)thiophene-2-carboxamides and identification of more stable class II histone deacetylase (HDAC) inhibitors

Bioorg Med Chem Lett. 2008 Dec 1;18(23):6078-82. doi: 10.1016/j.bmcl.2008.10.041. Epub 2008 Oct 12.

Abstract

5-(Trifluoroacetyl)thiophene-2-carboxamides were found to be potent and selective class II HDAC inhibitors. This paper describes their further development and the investigation on the cause for the lack of cell-based activity. A rapid screening assay was set up which enabled the identification of more metabolic stable compounds as potent and selective class II HDAC inhibitors.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Amides / pharmacology*
  • Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors
  • Cytochrome P-450 CYP2C9
  • Drug Design
  • HCT116 Cells
  • HeLa Cells
  • Hepatocytes / drug effects
  • Histone Deacetylase Inhibitors*
  • Histone Deacetylases / classification
  • Humans
  • Microsomes, Liver / drug effects
  • Molecular Structure
  • Structure-Activity Relationship
  • Thiophenes / chemical synthesis*
  • Thiophenes / chemistry
  • Thiophenes / pharmacology*
  • Tubulin / drug effects

Substances

  • Amides
  • Histone Deacetylase Inhibitors
  • Thiophenes
  • Tubulin
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • Histone Deacetylases