Estimation Of Lipophilicity And Design Of New 17 Beta-Carboxamide Glucocorticoids Using Rp-Hplc And Quantitative Structure-Retention Relationships Analysis

Eight 17 beta-carboxamide glucocorticoids with local anti-inflammatory activity were selected and their retention behavior tested in six RP-HPLC systems (I-VI). logkw, a, and phi(0) parameters were calculated and correlation with previously determined logPo/w values was examined. RP-HPLC system IV, which consisted of cyano column and methanol-water mobile phases (50:50, 60:40, 70:30, and 80:20, v/v), was selected as the most reliable for lipophilicity prediction and used for the analysis of chromatographic behavior of remaining fourteen 17 beta-carboxamide glucocorticoids. Quantitative structure-retention relationships analysis was performed and PIS(logkw) model was selected as the most statistically significant. On the basis of selected model and interpretation of corresponding descriptors, new derivatives with higher logkw values and higher expected lipophilicity were designed.