Design and synthesis of N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5- methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine [Muraglitazar/BMS-298585], a novel peroxisome proliferator-activated receptor alpha/gamma dual agonist with efficacious glucose and lipid-lowering activities

J Med Chem. 2005 Mar 24;48(6):2248-50. doi: 10.1021/jm0496436.

Abstract

Muraglitazar/BMS-298585 (2) has been identified as a non-thiazolidinedione PPAR alpha/gamma dual agonist that shows potent activity in vitro at human PPARalpha (EC(50) = 320 nM) and PPARgamma(EC(50) = 110 nM). Compound 2 shows excellent efficacy for lowering glucose, insulin, triglycerides, and free fatty acids in genetically obese, severely diabetic db/db mice and has a favorable ADME profile. Compound 2 is currently in clinical development for the treatment of type 2 diabetes and dyslipidemia.

MeSH terms

  • Adipocytes / cytology
  • Animals
  • Blood Glucose / drug effects
  • Cell Line
  • Diabetes Mellitus, Type 2 / drug therapy
  • Fatty Acids / blood
  • Glycine / analogs & derivatives*
  • Glycine / chemical synthesis*
  • Glycine / chemistry
  • Glycine / pharmacology
  • Humans
  • Hyperlipidemias / drug therapy
  • Hypoglycemic Agents / chemical synthesis*
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / pharmacology
  • Hypolipidemic Agents / chemical synthesis*
  • Hypolipidemic Agents / pharmacokinetics
  • Hypolipidemic Agents / pharmacology
  • Insulin / blood
  • Male
  • Mice
  • Mice, Obese
  • Oxazoles / chemical synthesis*
  • Oxazoles / chemistry
  • Oxazoles / pharmacology
  • PPAR alpha / agonists*
  • PPAR gamma / agonists*
  • Transcriptional Activation
  • Triglycerides / blood

Substances

  • Blood Glucose
  • Fatty Acids
  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • Insulin
  • Oxazoles
  • PPAR alpha
  • PPAR gamma
  • Triglycerides
  • Glycine
  • muraglitazar