Synthesis and nuclear factor-kappaB inhibitory activities of 6- or 7-methylchroman-2-carboxylic acid N-(substituted) phenylamides

Arch Pharm Res. 2009 Feb;32(2):167-75. doi: 10.1007/s12272-009-1131-3. Epub 2009 Mar 13.

Abstract

A series of 6- or 7-methylchroman-2-carboxylic acid N-(substituted) phenylamides (2a-s, 3a-s) were synthesized. Their abilities to inhibit nuclear factor-kappaB (NF-kappaB) activity were evaluated in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. Compounds with substituents such as -H, -CH(3), and -CF(3) on the phenyl ring were poor inhibitors of NF-kappaB. The most active NF-kappaB inhibitors contained 4-Cl (3s) and 4-OMe (3g) in the 7-methylchroman-2-carboxamide derivatives and 2-OH (2b) and 4-Cl (2s) in the 6-methylchroman-2-carboxamide derivatives (IC(50): 20.2-24.0 microM). These were slightly more potent than a reference compound, KL-1156 (1) (IC(50): 43.9 microM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chromans / chemical synthesis*
  • Chromans / chemistry
  • Chromans / pharmacology*
  • Inhibitory Concentration 50
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Molecular Structure
  • NF-kappa B / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

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