Discovery of novel quinoline carboxylic acid series as DGAT1 inhibitors

Bioorg Med Chem Lett. 2014 Apr 1;24(7):1790-4. doi: 10.1016/j.bmcl.2014.02.028. Epub 2014 Feb 19.

Abstract

Herein we report the design and synthesis of a series of novel bicyclic DGAT1 inhibitors with a carboxylic acid moiety. The optimization of the initial lead compound 7 based on in vitro and in vivo activity led to the discovery of potent indoline and quinoline classes of DGAT1 inhibitors. The structure-activity relationship studies of these novel series of bicyclic carboxylic acid derivatives as DGAT1 inhibitors are described.

Keywords: Cyclohexanecarboxylic acid; DGAT1 inhibitor; Diacylglycerol acyltransferase inhibitor; Indoline; Quinoline; Triacylglyceride.

MeSH terms

  • Animals
  • Carboxylic Acids / chemical synthesis
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / pharmacology*
  • Diacylglycerol O-Acyltransferase / antagonists & inhibitors*
  • Diacylglycerol O-Acyltransferase / metabolism
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Quinolones / chemical synthesis
  • Quinolones / chemistry
  • Quinolones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Carboxylic Acids
  • Enzyme Inhibitors
  • Quinolones
  • DGAT1 protein, human
  • Dgat1 protein, mouse
  • Diacylglycerol O-Acyltransferase