Design, synthesis, and structure-activity relationship study of peroxisome proliferator-activated receptor (PPAR) δ-selective ligands

Hiroyuki Miyachi

Research output: Contribution to journalReview article

13 Citations (Scopus)

Abstract

Improvements in our understanding of the functions of peroxisome proliferator-activated receptor (PPAR) subtypes as master regulators of many biological functions have made it possible to develop novel PPAR ligands with characteristic subtype selectivity as biochemical tools and/ or candidatedrugs for the treatment of PPAR-dependent diseases such as metabolic syndrome, which includes type II diabetes, dyslipidemia, obesity, hypertension, and inflammation. Based on the findings that the glitazone-class antidiabetic agents, and fibrate-class antidyslipidemic agents are ligands of PPARγ and PPARα: respectively, much research interest has been focused on these two subtypes as therapeutic targets for the treatment of type II diabetes and dyslipidemia. In contrast, research interest in PPARδ has, been limited. However, since 2001, the availability of PPARδ knockout animals and selective ligands has led to the uncovering of possible roles of PPARδ in fatty acid metabolism, insulin resistance, reverse cholesterol transport, inflammation, and so on. It has become clear that ligands able to modulate PPARδ-mediated pathways are candidates for the treatment of altered metabolic function. This review focuses on recent medicinal chemical studies to identify PPARδ-selective agonists.

Original languageEnglish
Pages (from-to)2335-2343
Number of pages9
JournalCurrent Medicinal Chemistry
Volume14
Issue number22
DOIs
Publication statusPublished - Sep 1 2007

Keywords

  • GW-501516
  • Metabolic syndrome
  • PPAR
  • PPARδ
  • PPARδ selective agonist
  • Peroxisome proliferator-activated receptor
  • TIPP-204

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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