The Influence of Bioisosteres in Drug Design: Tactical Applications to Address Developability Problems

The application of bioisosteres in drug discovery is a well-established design concept that has demonstrated utility as an approach to solving a range of problems that affect candidate optimization, progression, and durability. In this chapter, the application of isosteric substitution is explored in a fashion that focuses on the development of practical solutions to problems that are encountered in typical optimization campaigns. The role of bioisosteres to affect intrinsic potency and selectivity, influence conformation, solve problems associated with drug developability, including P-glycoprotein recognition, modulating basicity, solubility, and lipophilicity, and to address issues associated with metabolism and toxicity is used as the underlying theme to capture a spectrum of creative applications of structural emulation in the design of drug candidates.