Structure-activity relationships of 6-hydroxy-7-methoxychroman-2-carboxylic acid N-(substituted)phenylamides as inhibitors of nuclear factor-kappaB activation

Arch Pharm Res. 2007 Oct;30(10):1210-5. doi: 10.1007/BF02980261.

Abstract

A series of 6-hydroxy-7-methoxychroman-2-carboxylic acid N-substitutedphenylamides (2a-n) were synthesized and their ability to inhibit nuclear factor-kappaB activity was evaluated in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. While compounds bearing -OH, or -OCH3 substituents were inactive, compounds with -CH3, -CF3, or -Cl substituents were potent inhibitors (IC50: 6.0-60.2 microM). The most active compound, 2n, contained a 4-Cl substituent on the phenyl ring and was four times more potent than the compound KL-1156.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Chromans / chemistry
  • Chromans / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • Molecular Structure
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Structure-Activity Relationship
  • Transcription, Genetic / drug effects*
  • Transfection

Substances

  • 6-hydroxy-7-methoxychroman-2-carboxylic acid phenylamide
  • Anti-Inflammatory Agents
  • Chromans
  • Lipopolysaccharides
  • NF-kappa B