56355-47-6Relevant academic research and scientific papers
Antileukotrienic phenethylamido derivatives of arylalkanoic acids in the treatment of ulcerative colitis
Junek, Richard,Kverka, Miloslav,Jandera, Antonin,Panajotova, Vladimira,Satinsky, Dalibor,Machacek, Milos,Kuchar, Miroslav
experimental part, p. 332 - 344 (2009/04/06)
A series of arylalkanoic acid derivatives bearing methyl(phenethyl)amino groups were prepared and their inhibition of LTB4 biosynthesis was evaluated. Regression analysis showed the slightly different parabolic dependences of this activity on lipophilicity of α-methyl and α-unsubstituted alkanoic acid derivatives. The relationship derived for α-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 log Popt (=6.97). But generally, the structural changes in the acidic part of compounds under study did not yield the substantial improvement of LTB4 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 LTB4 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.
THE SYNTHESIS OF ARYLPROPIONIC ACIDS AND THE QUANTITATIVE RELATIONSHIP BETWEEN THE STRUCTURE AND THE ACTIVATION OF FIBRINOLYSIS
Kuchar, Miroslav,Brunova, Bohumila,Rejholec, Vaclav,Roubal, Zdenek,Nemecek, Oldrich
, p. 1173 - 1187 (2007/10/02)
A number of substituted 2-arylpropionic (IV) and 3-arylpropionic (V) acids were prepared and their activity in the activation of fibrinolysis and the inhibition of heat denaturation of serum albumin was evaluated.The results were worked up using the method of regression analysis.From the regression equation obtained it may be considered that both activities are affected mainly by the lipophilicity of the aromatic substituents.The effect of branching in the connecting chain between the carboxyl group and the aromatic ring is negligible in both activities.Thelinear dependence of the fibrinolytic capacity on lipophilicity is in both series of acids, IV and V, characterized by a distinct decrease in activity, following the attainment of the optimum value of lipophilicity.In the series of cinnamic acids (VI) regression equations concerning the inhibition of the denaturation of serum albumin and the activation of fibrinolysis were also calculated, showing a linear dependence of these activities on the lipophilicity of the varying substituents R and X.Summary regression equations were derived for both activities in the whole set of acids I-VI.Both the inhibition of the denaturation of serum albumin , and the activation of fibrinolysis depends on the lipophilicity of the mentioned acids exclusively.The modification of the connecting chain between the carboxyl group and the aromatic ring affects both activities primarily by the corresponding change in lipophilicity.
