Lead Quality
J. Willem M. Nissink, Sébastien L. Degorce, Ken Page · Methods and principles in medicinal chemistry · 2016
This chapter explores how quality is generally defined in leads and, ultimately, drugs, and how this quest for quality influences design strategy and project progress. It overviews the types of assays that are typically at the disposal of the medicinal chemist to characterize efficacy, physicochemical properties, safety, and drug metabolism and pharmacokinetics (DMPK). The chapter highlights a number of rules and guidelines that are commonplace in early-stage drug design, and discusses how these are used to maximize the chances that the drug will be efficacious, safe, and can be administered in a suitable fashion. It illustrates an alternative method for assessing compound quality in the context of oral human exposure, through prediction of human oral dose estimates i.e. estimated dose to man (eD2M), at an early stage in a drug design project.