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Antileukotrienic N-arylethyl-2-arylacetamides in the treatment of ulcerative colitis
Richard Junek1, Bohumila Brůnová, Miloslav Kverka
1Zentiva VUFB, a.s., 102 01 Prague 10, Czech Republic.
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.
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