Structural pairwise comparisons of HLM stability of phenyl derivatives: Introduction of the Pfizer metabolism index (PMI) and metabolism-lipophilicity efficiency (MLE)

Data mining by pairwise comparison of over 150,000 human liver microsome (HLM) intrinsic clearance values stored within the internal Pfizer database has been performed by an automated tool. Systematic probability tables of specific structural changes on the intrinsic clearance of phenyl derivatives have been generated. From these data two new parameters, the Pfizer Metabolism Index (PMI) and Metabolism-Lipophilicity Efficiency (MLE) are introduced for each fragment. The findings are applied to a Topliss style analysis that focuses on metabolic stability.