Design and synthesis of benzoxazole containing indole analogs as peroxisome proliferator-activated receptor-γ/δ dual agonists

Bioorg Med Chem Lett. 2011 May 15;21(10):3057-61. doi: 10.1016/j.bmcl.2011.03.027. Epub 2011 Mar 24.

Abstract

A series of benzoxazole or benzothiazole containing indole analogs, 6-alkoxyindole-2-carboxylic acids and 5-alkoxy-3-indolylacetic acids, were synthesized as novel candidates of PPARγ/δ dual agonists and their ligand activities for PPAR subtypes (α, γ, and δ) were investigated. In transient transactivation assay, several compounds activated PPARγ and δ with little activity of PPARα. Putative binding mode of the compounds 1a and 2a in the active site of PPARγ was similar with that of rosiglitazone and the molecular modeling provides molecular insight to the observed activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemical synthesis
  • Acetates / chemistry
  • Acetates / pharmacology
  • Benzoxazoles / chemical synthesis*
  • Benzoxazoles / chemistry
  • Benzoxazoles / pharmacology*
  • Carboxylic Acids / chemical synthesis
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / pharmacology
  • Drug Design*
  • Indoles / chemistry*
  • Molecular Structure
  • PPAR gamma / agonists*
  • Protein Binding / drug effects

Substances

  • Acetates
  • Benzoxazoles
  • Carboxylic Acids
  • Indoles
  • PPAR gamma