Design and synthesis of potent carboxylic acid DGAT1 inhibitors with high cell permeability

Bioorg Med Chem Lett. 2012 Jan 15;22(2):824-8. doi: 10.1016/j.bmcl.2011.12.050. Epub 2011 Dec 17.


A series of potent carboxylic acid DGAT1 inhibitors with high permeability were developed from a virtual screening hit. Strategies were employed to reduce Pgp substrate recognition and increase passive permeability, resulting in the discovery of a series showing good inhibition of cellular triglyceride synthesis. The mutagenic potential of prospective metabolites was evaluated in the Ames assay, and one aniline was shown to be devoid of mutagenicity.

MeSH terms

  • Caco-2 Cells
  • Diacylglycerol O-Acyltransferase / antagonists & inhibitors*
  • Diacylglycerol O-Acyltransferase / metabolism
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Permeability / drug effects
  • Structure-Activity Relationship


  • Enzyme Inhibitors
  • DGAT1 protein, human
  • Diacylglycerol O-Acyltransferase