A matched molecular pair analysis of in vitro human microsomal metabolic stability measurements for methylene substitution or replacements – identification of those transforms more likely to have beneficial effects

Abstract

A matched molecular pair analysis (MMPA) was used to study the classic medicinal chemistry transformations of a methylene (–CH₂–) into metabolic blocking groups. 1826 matched pairs were identified for 24 transforms and in vitro human microsomal stability analysed. Of these, 4 transforms have shown significant beneficial increase in stability, suggesting these transforms as preferred changes during compound optimisation.