Role of Structural Modifications of Drug Candidates to Enhance Metabolic Stability
Ala F. Nassar · 2022
The activity–exposure–toxicity relationship, which can be described as “the rule of three,” presents the single most difficult challenge in the design and advancement of drug candidates to the development stage. Absorption, distribution, metabolism, and excretion (ADME) studies are widely used in drug discovery to optimize this balance of properties necessary to convert leads into drugs which are both safe and effective for human patients. Metabolite characterization has become one of the main drivers of the drug discovery process, helping to optimize ADME properties and increase the success rate for drugs. In this chapter, we will address strategies for the decision-making process in structural modification of drug candidates to reduce metabolic instability. Several examples are included to show how metabolic stability has influenced and guided drug design.