Application of biopartitioning micellar chromatography and QSRR modeling for prediction of gastrointestinal absorption and design of novel β-hydroxy-β-arylalkanoic acids

Abstract Gastrointestinal absorption of thirteen novel β-hydroxy-β-arylalkanoic acids (HAA) with anti-inflammatory activity was predicted by use of biopartitioning micellar chromatography and compared to ibuprofen. All tested HAA have lower retention factors ( k ) and lower expected gastrointestinal absorption than ibuprofen, whereas derivatives with the highest values of k are 1C, 2APTF and 2C. Quantitative structure-retention relationship (QSRR) analysis was performed in order to identify molecular descriptors with the highest influence on k and ANN( k ) model was selected as optimal. Descriptors which form this model (nBM, P_VSA_LogP_8 and Eta_L) indicate that replacement of phenyl ring with a saturated or partially unsaturated one, as well as presence of halogens and nitro group should positively affect k values. On the basis of these conclusions, six novel HAA were designed and selected QSRR model was used for the prediction of their k values.