Bioisosteres

This chapter discusses what medicinal chemists do every day: take the original hits and improve them to lead compounds, drug candidates, and ultimately drugs. The concept of bioisosteres is a good guide for investigating the structure–activity relationship and many other relevant drug-likeness attributes. The objective of a bioisosteric replacement is to create a new compound with similar biological properties to the parent compound. The bioisosteric replacement may be physiochemically or topologically based. Deuterium, fluorine, and chlorine atoms, as well as the methyl group, are popular isosteres of hydrogen. Many fat molecules are linear or branched aliphatic acids and they are catabolized via a mechanism known as β-oxidation. If a drug, such as prostaglandins, contains a linear or branched aliphatic acid, it is understandably subjected to the same metabolism of β-oxidation cycle and its bioavailability may suffer.