Antileukotrienic N-arylethyl-2-arylacetamides in the treatment of ulcerative colitis

Eur J Med Chem. 2007 Aug;42(8):1084-94. doi: 10.1016/j.ejmech.2007.01.014. Epub 2007 Jan 27.

Abstract

A series of arylacetic acid derivatives bearing methyl(arylethyl)amino groups were prepared and their antileukotrienic activities involving LTB(4) were evaluated. Regression analysis has shown a strong dependence of these activities on lipophilicity for both LTB(4) receptor binding and inhibition of LTB(4) biosynthesis; parabolic relationships were derived. The values of slopes of the ascending linear parts of these dependences indicate various types of hydrophobic binding at the site of ligand interaction with relevant biomacromolecules. The anti-inflammatory effect of the compounds under study was also evaluated in three animal models of inflammation and their possible utilization in the treatment of ulcerative colitis (UC) was followed. The importance of antileukotrienic activities for the anti-inflammatory effect, especially in the model of UC was discussed, but further experiments are necessary to confirm the respective relations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / chemical synthesis*
  • Acetamides / pharmacology*
  • Acetamides / therapeutic use
  • Animals
  • Colitis, Ulcerative / drug therapy*
  • Disease Models, Animal
  • Edema / chemically induced
  • Edema / drug therapy
  • Hydrophobic and Hydrophilic Interactions
  • Leukotriene B4 / antagonists & inhibitors*
  • Leukotriene B4 / biosynthesis
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Rats
  • Receptors, Leukotriene B4 / antagonists & inhibitors
  • Receptors, Leukotriene B4 / metabolism
  • Structure-Activity Relationship

Substances

  • Acetamides
  • Receptors, Leukotriene B4
  • Leukotriene B4