Discovery of N-arylpyrroles as agonists of GPR120 for the treatment of type II diabetes

Bioorg Med Chem Lett. 2018 Mar 1;28(5):841-846. doi: 10.1016/j.bmcl.2018.02.013. Epub 2018 Feb 8.

Abstract

The discovery of a novel series of N-arylpyrroles as agonists of GPR120 (FFAR4) is discussed. One lead compound is a potent GPR120 agonist, has good selectivity for related receptor GPR40 (FFAR1), has acceptable PK properties, and is active in 2 models of Type 2 Diabetes in mice.

Keywords: DIO mouse; FFAR4; GPR120; GPR40; N-arylpyrrole; Type 2 diabetes; oGTT.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Humans
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology*
  • Mice
  • Molecular Structure
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry
  • Pyrroles / pharmacology*
  • Receptors, G-Protein-Coupled / agonists*
  • Structure-Activity Relationship

Substances

  • FFAR4 protein, human
  • Hypoglycemic Agents
  • Pyrroles
  • Receptors, G-Protein-Coupled