Prediction of Lipophilicity and Pharmacokinetics of Chloroacetamides by Chemometric Approach

Iranian Journal of Pharmaceutical Research

关键词: N-(substituted phenyl)-2-chloroacetamides;    Lipophilicity;    RPTLC;    Pharmacokinetic predictors;    Cluster Analysis;    Principal component analysis;   

DOI  :  

学科分类：社会科学、人文和艺术（综合）

来源: Shaheed Beheshti Medical University * School of Pharmacy

【 摘 要 】

In this study, the existence of biological potential of selected N-(substituted phenyl)-2-chloroacetamides was examined none empirically, as was the possibility of applying simpleexperimental technique in predicting essential properties which affect the biological activityof the compounds. By applying the Lipinski and Ghose’s rules, it has been revealed that theexamined chloroacetamides fulfill the theoretical requirements for bioactive compounds.In addition, lipophilicity was determined by applying the reversed-phase thin-layerchromatography (RPTLC18F254s) in the mixtures of water and two organic modifiers separately(methanol and acetone) and by using relevant software packages. The chromatographicretention parameters, RM0 and m, as the presumed criteria for the lipophilicity of the examinedchloroacetamides were correlated by linear regression analysis, and the relevant chemometricmethods (Cluster Analysis and Principal Component Analysis) with the standard measure oflipophilicity, log P, and with the selected pharmacokinetic predictors. Thus good correlationsin both water-modifier systems (average correlation coefficients, r , 0.947 and 0.931) wereobtained. The chemometric methods, as well as the classical correlation methods gave similarresults which demonstrated that the chromatographic retention parameters, RM0 and m, cansuccessfully describe the lipophilicity and the pharmacokinetics of the N-(substituted phenyl)-2-chloroacetamides in the first steps of preclinical research.

【 授权许可】

CC BY