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

A series of arylacetic acid derivatives bearing methyl(arylethyl)amino groups were prepared and their antileukotrienic activities involving LTB4 were evaluated. Regression analysis has shown a strong dependence of these activities on lipophilicity for both LTB4 receptor binding and inhibition of LTB4 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.

The new N-arylethyl-2-arylacetamides 1–9 were synthesized and their antileukotrienic (in vitro) and anti-inflammatory (in vivo) activities were determined. Analysis of QSAR of antileukotrienic activities was performed. Some compounds were more active in the treatment of ulcerative colitis than standard sulfasalazine.Figure optionsDownload as PowerPoint slide