A series of arylalkanoic acid derivatives bearing methyl(phenethyl)amino groups were prepared and their inhibition of LTB(4) biosynthesis was evaluated. Regression analysis showed the slightly different parabolic dependences of this activity on lipophilicity of alpha-methyl and alpha-unsubstituted alkanoic acid derivatives. The relationship derived for alpha-unsubstituted alkanoic acids was extended by previously prepared group of similar derivatives of arylacetic acids without any change of regression coefficients and statistical criteria. It was concluded that the most active compounds belong to 2-arylpropanoic acid derivatives with lipophilicity close to logP(opt) (=6.97). But generally, the structural changes in the acidic part of compounds under study did not yield the substantial improvement of LTB(4) biosynthesis inhibition in comparison with the previously prepared series of derivatives IV. The anti-inflammatory effect of the compounds under study was evaluated in three animal models of inflammation and their possible utilization in the treatment of ulcerative colitis (UC) was followed. From 12 evaluated compounds, 4 compounds are more active in UC inhibition than the standard sulfasalazine but it can be stated that the change of connecting chain between aromatic ring and carboxyl did not bring about the important improvement of this activity in comparison with previous derivatives of arylacetic acids. Possible relation between LTB(4) biosynthesis inhibition and ulcerative colitis is seriously broken by the compound 8a with carbonyl as the additional functional group on the connecting chain between carboxyl and aromatic ring.

• MeSH
• antiflogistika farmakologie   chemická syntéza   MeSH
• aromatické uhlovodíky farmakologie   chemická syntéza   MeSH
• financování organizované MeSH
• gastrointestinální látky farmakologie   chemická syntéza   MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• kvantitativní vztahy mezi strukturou a aktivitou MeSH
• kyseliny karboxylové MeSH
• leukocyty MeSH
• receptory leukotrienu B4 antagonisté a inhibitory   MeSH
• ulcerózní kolitida farmakoterapie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zánět farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

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.

• MeSH
• acetamidy farmakologie   chemická syntéza   terapeutické užití   MeSH
• edém farmakoterapie   chemicky indukované   MeSH
• financování organizované MeSH
• hydrofobní a hydrofilní interakce MeSH
• krysa rodu rattus MeSH
• leukotrien B4 antagonisté a inhibitory   biosyntéza   MeSH
• modely nemocí na zvířatech MeSH
• neutrofily metabolismus   účinky léků   MeSH
• receptory leukotrienu B4 antagonisté a inhibitory   metabolismus   MeSH
• ulcerózní kolitida farmakoterapie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH