title: Structural pairwise comparisons of HLM stability of phenyl derivatives: Introduction of the Pfizer metabolism index (PMI) and metabolism-lipophilicity efficiency (MLE).
abstract: 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.
authors.affiliation: Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer PGRD, Sandwich, Kent CT139NJ, United Kingdom. mark.l.lewis@pfizer.com
authors.forename: Mark L
authors.initials: ML
authors.lastname: Lewis
authors.forename: Lourdes
authors.initials: L
authors.lastname: Cucurull-Sanchez
mesh_terms: D000465:Algorithms; D001555:Benzene Derivatives / Q000493:pharmacokinetics*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D008657:Metabolic Clearance Rate; D053858:Metabolic Networks and Pathways; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D001555:Benzene Derivatives; D003577:Cytochrome P-450 Enzyme System