Design, synthesis and SAR of a novel series of heterocyclic phenylpropanoic acids as GPR120 agonists

Bioorg Med Chem Lett. 2017 Aug 1;27(15):3272-3278. doi: 10.1016/j.bmcl.2017.06.028. Epub 2017 Jun 12.

Abstract

A novel series of 5-membered heterocycle-containing phenylpropanoic acid derivatives was discovered as potent GPR120 agonists with low clearance, high oral bioavailability and in vivo antidiabetic activity in rodents.

Keywords: GPR120; Phenylpropanoic acid; Type 2 diabetes.

MeSH terms

  • Animals
  • Biological Availability
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Design
  • HEK293 Cells
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacokinetics
  • Heterocyclic Compounds / pharmacology
  • Heterocyclic Compounds / therapeutic use
  • Humans
  • Hypoglycemic Agents / chemistry*
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Mice, Inbred C57BL
  • Phenylpropionates / chemistry*
  • Phenylpropionates / pharmacokinetics
  • Phenylpropionates / pharmacology*
  • Phenylpropionates / therapeutic use
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / metabolism
  • Structure-Activity Relationship

Substances

  • Blood Glucose
  • FFAR4 protein, human
  • Heterocyclic Compounds
  • Hypoglycemic Agents
  • Phenylpropionates
  • Receptors, G-Protein-Coupled
  • 3-phenylpropionic acid