Design and synthesis of alkoxyindolyl-3-acetic acid analogs as peroxisome proliferator-activated receptor-γ/δ agonists

Bioorg Med Chem Lett. 2013 Jan 15;23(2):513-7. doi: 10.1016/j.bmcl.2012.11.033. Epub 2012 Nov 22.

Abstract

A series of carbazole or phenoxazine containing alkoxyindole-3-acetic acid analogs were prepared as PPARγ/δ agonists and their transactivation activities for PPAR receptor subtypes (α, γ and δ) were investigated. Structure-activity relationship studies disclosed the effect of the lipophilic tail, attaching position of the alkoxy group and N-benzyl substitution at indole. Compound 1b was the most potent for PPARδ and 3b for PPARγ. Molecular modeling suggested two different binding modes of our alkoxyindole-3-acetic acid analogs providing the insight into their PPAR activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetic Acid / chemical synthesis*
  • Acetic Acid / chemistry
  • Acetic Acid / pharmacology
  • Alcohols / chemical synthesis*
  • Alcohols / chemistry
  • Alcohols / pharmacology
  • Drug Design*
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • PPAR delta / agonists*
  • PPAR gamma / agonists*
  • Protein Binding / drug effects
  • Structure-Activity Relationship

Substances

  • Alcohols
  • Indoles
  • PPAR delta
  • PPAR gamma
  • alkoxyl radical
  • Acetic Acid