Search Results

You are looking at 1 - 3 of 3 items for

  • Author or Editor: Gyongyi Vastag x
  • Refine by Access: All Content x
Clear All Modify Search

It has been established that the selected acetamide derivatives fulfill Veber’s and Pardridge’s rule of good bioavailability. The lipophilicity as a crucial molecular descriptor of biological activity for acetamide derivatives was determined by reversed-phase thinlayer chromatography (RP-TLC) in different mixtures of water and organic modifiers (ethanol and tetrahydrofuran). Also, lipophilicity was examined mathematically, by using relevant software packages. The effects of the substituent on the lipophilicity of acetamide derivatives were analyzed. By applying linear regression analysis and 2 multivariate methods (cluster analysis and principal component analysis), the obtained chromatographic parameters, R M 0 and m, of the examined acetamides were correlated with the standard measure of lipophilicity, log P, important pharmacokinetic predictors, and selected toxicity parameters. The obtained results confirmed that chromatographic parameters, R M 0 and m, determined by RP-TLC, could be successfully used for describing the lipophilicity and estimation of pharmacokinetics and the toxic effects of the studied acetamide derivatives.

Restricted access

The chromatographic behavior of some N,N -disubstituted-2-phenylaccetamide derivatives has been studied on the chemically bonded stationary phase RP-C 18 with acetone, acetonitrile, tetrahydrofuran, dioxane, methanol, ethanol, 1-propanol, and 2-propanol as organic modifiers of aqueous mobile phases. The retention observed with different mobile-phase modifiers was correlated. The effects of different physicochemical properties of the compounds on retention behavior when chromatographed with aqueous mobile phases containing protic and aprotic modifiers were also studied. Multiple linear regression analysis was used to correlate chromatographic retention constants of the compounds with physicochemical properties. The chromatographic lipophilicity R M 0 (determined by linear extrapolation) was correlated with log P values calculated by use of different theoretical methods. Good relationships were obtained for all the systems investigated. Good correlation was obtained between lipophilicity measured chromatographically and biological activity predictors.

Restricted access

Modeling properties of newly synthesized compounds is important for both understanding their activity and predicting their interactions. This paper describes the evaluation of the lipophilicity of the newly synthesized cycloalkylspiro-5-hydantoins by experimental and calculation methods. The chromatographic lipophilicity (R M 0) of the analyzed compounds was determined by reversed-phase liquid chromatographic system consisting of RP-18 stationary phase and methanol—water mobile phase. Correlation coefficients between R M 0 values and the predicted log P were above 0.93, indicating a strong linear relationship between the variables. Multivariate data analysis applied in this study enabled the comparison of the lipophilicity and the structure of the investigated compounds using solely information obtained from thin-layer chromatography. Hierarchical clustering analysis (HCA) reveals a high similarity between R M 0 and miLogP whereas squared log Ps such as ALOGP2 and MLOGP2 were distinct from R M 0. HCA classifies the investigated compounds into three clusters according to lipophilicity. Principal component analysis (PCA) yields two principal components which explained >99.19% total variance. The changes in the lipophilicity of the substituents attached in the molecule are reflected in the value of PCs. An increase in the lipophilicity of spiro substituent results in a decrease of values of both PC1 and PC2. The increase in the lipophilicity of R substituent decreases the value of PC1 and increases the value of PC2. The positive value of PC1 is typical for the compounds with the electron withdrawing groups such as CN, NO 2 , or OCH 3 .

Restricted access