Structural basis for the structure-activity relationships of peroxisome proliferator-activated receptor agonists

J Med Chem. 2006 Oct 19;49(21):6421-4. doi: 10.1021/jm060663c.

Abstract

Type 2 diabetes has rapidly reached an epidemic proportion becoming a major threat to global public health. PPAR agonists have emerged as a leading class of oral antidiabetic drugs. We report a structure biology analysis of novel indole-based PPAR agonists to explain the structure-activity relationships and present a critical analysis of reasons for change in selectivity with change in the orientation of the same scaffolds. The results would be helpful in designing novel PPAR agonists.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemistry
  • Alkylation
  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • In Vitro Techniques
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / pharmacology
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Naphthalenes / chemical synthesis
  • Naphthalenes / chemistry
  • Naphthalenes / pharmacology
  • Peroxisome Proliferator-Activated Receptors / agonists*
  • Peroxisome Proliferator-Activated Receptors / chemistry*
  • Peroxisome Proliferator-Activated Receptors / genetics
  • Propionates / chemistry
  • Structure-Activity Relationship
  • Thermodynamics
  • Transcriptional Activation / drug effects

Substances

  • Acetates
  • Indoles
  • Ligands
  • Naphthalenes
  • Peroxisome Proliferator-Activated Receptors
  • Propionates