The quantitative relationships of the partition coefficients calculated in the series of n-r-amine functional derivatives

Abstract

Using on-line services and the ChemBioOffice2014 software package the values of the partition coefficients of some N-R-amine derivatives have been calculated. To identify the quantitative relationships and select the optimal algorithm of calculations the correlation and regression analysis of the values obtained has been conducted. Statistically significant values of correlation for the partition coefficients calculated have been determined. It has been shown that it is advisable to use the value AlogPs for further application.Lipophilicity is one of the criteria for assessing the similarity of synthetic substances and drugs, and it affects the biological activity of substances [9,13,14]. The partition coefficient of n-octanol-water (logP) characterizes physicochemical properties of substances in solutions and is used to simulate their behaviour in the body [3,14]. Distribution and redistribution of substances between lipophilic (fatty) and aqueous phases are part of biological processes, in particular transmembrane transport through lipid layers [11]. Hydrophobicity plays an important role in determining distribution of a substance in the body after absorption, its metabolic rate and elimination. The hydrophobic effect is essential for binding of drugs with their receptors [13].The ability to predict biological properties of compounds through their lipophilicity allows to optimize the search for new drugs and is often included in equations for calculations of the quantitative structure -activity relationships (QSAR) [16].The value logP is experimentally determined by the classical method of measuring distribution of organic compounds between the non-polar phase and water [14] using chromatographic [18], electrochemical [23] and other methods.However, experimental methods to determine logP are time-consuming and expensive, and the values obtained often differ due to the influence of many factors. Therefore, today a significant number of algorithms for theoretical calculations of values logP implemented using the appropriate software [5, 6, 8, 17,24, 25].The values of the partition coefficients of n-octanolwater experimentally obtained with the values theoretically calculated by different algorithms (AlogPs, IAlogP, ClogP, miLogP, logP KowWIN , xlogP3, etc.) were compared for 193 substances [19] and more than 96 000 compounds (including databases of Nykomed and Pfizer) [15]. In both studies the experimental data better correlate with the methods of AlogPs, xlogP3, logP KowWIN .Attempts to achieve proportionality of results of the theoretical calculation methods of prediction and the experimental determination of lipophilicity of organic compounds are still relevant in modern scientific studies [1, 16, 22].The aim of this work is to determine the mutual correlation of the values of the partition coefficients in the series of some functional derivatives of N-R-amines (1-21) calculated by different algorithms. Materials and MethodsTaking into account the data [15,19] we used the available free on-line methods xlog...

Molecular parameters and the antimicrobial activity of functional derivatives of n-,r-amines

“…1) was studied, the values of the distribution coefficients for these compounds were calculated [9]. Using the values obtained the possible quantitative relationships were determined, and the "structureaction" relationships in the given series compared to the data of the biological activity experimentally obtained were discussed.…”