Phenylacetic acid derivatives as hPPAR agonists

Bioorg Med Chem Lett. 2003 Apr 7;13(7):1277-80. doi: 10.1016/s0960-894x(03)00115-x.

Abstract

Beginning with the weakly active lead structure 1, a new series of hPPAR agonists was developed. In vivo glucose and triglyceride lowering activity was obtained by homologation and oxamination to 3, then conversion to substituted benzisoxazoles 4 and 5. Further manipulation afforded benzofurans 6 and 7. Compound 7 was of comparable potency as a glucose and triglyceride lowering agent in insulin resistant rodents to BRL 49653.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Dose-Response Relationship, Drug
  • Drug Design
  • Hypoglycemic Agents / chemical synthesis*
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / pharmacology*
  • Insulin Resistance
  • Male
  • Mice
  • Phenylacetates / chemical synthesis*
  • Phenylacetates / pharmacokinetics
  • Phenylacetates / pharmacology*
  • Rats
  • Rats, Zucker
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Rosiglitazone
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Transcription Factors / agonists*
  • Triglycerides / blood

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Phenylacetates
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Triglycerides
  • Rosiglitazone