Synthesis and biological activity of novel alpha-substituted beta-phenylpropionic acids having pyridin-2-ylphenyl moiety as antihyperglycemic agents

Bioorg Med Chem. 2004 May 1;12(9):2419-39. doi: 10.1016/j.bmc.2004.01.048.

Abstract

We previously reported the identification of novel oximes having 5-benzyl-2,4-thiazolidinedione with antihyperglycemic activity. We now report the synthesis and biological activity of a novel series of oximes and amides having alpha-substituted-beta-phenylpropionic acids. In this series, we obtained potent PPAR alpha/gamma dual agonist (S)-9d, with which activation of PPAR alpha and PPAR gamma was considerably more potent than that of the reference compounds GW9578 22 and rosiglitazone 3, respectively. This means (S)-9d is of the strongest class of PPAR alpha/gamma dual agonists. In the course of this study, we also obtained 8h, which indicated potent plasma glucose lowering effect in spite of weak PPAR alpha/gamma agonistic activity.

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • DNA Primers
  • Humans
  • Hypoglycemic Agents / chemical synthesis*
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology*
  • Peroxisome Proliferator-Activated Receptors / agonists
  • Phenylpropionates / chemical synthesis*
  • Phenylpropionates / chemistry
  • Phenylpropionates / pharmacology*
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Spectrum Analysis

Substances

  • DNA Primers
  • Hypoglycemic Agents
  • Peroxisome Proliferator-Activated Receptors
  • Phenylpropionates
  • Pyridines
  • 3-phenylpropionic acid