Applications of Bioisosteres in the Design of Biologically Active Compounds

The design of bioisosteres represents a creative and productive approach to improve a molecule, including by enhancing potency, addressing pharmacokinetic challenges, reducing off-target liabilities, and productively modulating physicochemical properties. Bioisosterism is a principle exploited in the design of bioactive compounds of interest to both medicinal and agricultural chemists, and in this review, we provide a synopsis of applications where this kind of molecular editing has proved to be advantageous in molecule optimization. The examples selected for discussion focus on bioisosteres of carboxylic acids, applications of fluorine and fluorinated motifs in compound design, some applications of the sulfoximine functionality, the design of bioisosteres of drug-H2O complexes, and the design of bioisosteres of the phenyl ring.