Revisiting glitazars: thiophene substituted oxazole containing α-ethoxy phenylpropanoic acid derivatives as highly potent PPARα/γ dual agonists devoid of adverse effects in rodents

Bioorg Med Chem Lett. 2011 May 15;21(10):3103-9. doi: 10.1016/j.bmcl.2011.03.020. Epub 2011 Mar 28.

Abstract

In an effort to develop safe and efficacious compounds for the treatment of metabolic disorders, novel thiophene substituted oxazole containing α-alkoxy-phenylpropanoic acid derivatives are designed as highly potent PPARα/γ dual agonists. These compounds were found to be efficacious at picomolar concentrations. Lead compound 18d has emerged as very potent PPARα/γ dual agonist demonstrating potent antidiabetic and lipid lowering activity at a very low dose and did not exhibit any significant signs of toxicity in rodents.

MeSH terms

  • Administration, Oral
  • Animals
  • Cell Line
  • Dose-Response Relationship, Drug
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology
  • Inhibitory Concentration 50
  • Mice
  • Molecular Structure
  • Oxazoles / chemistry
  • PPAR alpha / agonists*
  • PPAR gamma / agonists*
  • Phenylpropionates / chemical synthesis*
  • Phenylpropionates / chemistry
  • Phenylpropionates / pharmacology*
  • Protein Binding / drug effects
  • Rats
  • Rats, Wistar
  • Rosiglitazone
  • Thiazolidinediones / chemical synthesis
  • Thiazolidinediones / chemistry
  • Thiazolidinediones / pharmacology
  • Thiophenes / chemistry

Substances

  • Hypoglycemic Agents
  • Oxazoles
  • PPAR alpha
  • PPAR gamma
  • Phenylpropionates
  • Thiazolidinediones
  • Thiophenes
  • Rosiglitazone