Studies on logP, retention time and QSAR of 2-substituted phenylnitronyl nitroxides as free radical scavengers.

As reported in our previous paper [Y. Wu, L. Bi, W. Bi, Z. Li, M. Zhao, C. Wang, J. Ju, S. Peng, Bioorg. Med. Chem. 14 (2006) 5711-5720.], a series of novel 2-substituted nitronyl nitroxides were synthesized and characterized to show enhanced free radical scavenger properties. Here, the logP values and retention time (alternatively represented as logK) of these 20 compounds were determined by the shake-flask method and HPLC analysis, respectively. We found that the prediction of logP directly from the measured logK value can result in a high accuracy, thus the determination of time-consuming logP can be replaced by the simple HPLC analysis. Using the conventional Hansch method, the QSAR equations of these nitronyl nitroxides were established to predict their capability of trapping free radicals such as *NO, *H(2)O(2) and *OH. Although the overall predictive accuracy is reasonable, it was found that the logP values for the compounds are not significantly related to their capability of trapping free radicals. Moreover, an improved QSAR analysis was performed by choosing new molecular descriptors generated from e-dragon server. The increased predictive accuracy suggests that these new QSAR models have practical application in screening new potential scavengers from the derivatives of 2-substituted phenylnitronyl nitroxides.