Bioisosterism is a molecular modification Medicinal Chemistry strategy
applied during drug design projects when a lead compound is available. The idea of
bioisisterism is centered at the use of chemical diversity in order to optimize
pharmaceutical properties of lead compounds and generate active analogs, replacing
problematic substructures inside lead compounds by others with similar
physicochemical properties that can improve the limitations observed for the original
lead compound. Bioisosterism can be a useful strategy in order to optimize lead
compounds searching for analogs with better selectivity and synthetic accessibility,
decreased toxicity, improved pharmacokinetics, enhanced solubility and metabolic
stability. This chapter highlights the computational approaches used to identify potential
bioisosters, discusses how bioisosterism can be helpful during the design of molecules
with better synthetic accessibility, and reviews the scaffold hopping technique, a novel
trend of bioisosterism application intended to identify interchangeable scaffolds among
pharmaceutical interesting molecules.
Keywords: Bioactivity, bioisosteric replacements, bioisosterism, chemoinformatics,
drug design, drug metabolism, intermolecular interactions, lead compounds,
medicinal chemistry, molecular descriptors, molecular modeling, scaffold hopping,
synthetic accessibility, toxicity, virtual screening.
