bioisosterie

Bioisosterism, or bioisosterie, is a strategy in medicinal chemistry in which one part of a molecule is replaced by another atom or group with similar physical or chemical properties. The goal is to retain the biological activity of the compound while altering properties such as potency, selectivity, metabolic stability, pharmacokinetics, or toxicity. The concept, developed in the mid-20th century, categorizes substituents by their ability to mimic key features that drive a molecule's interactions with biological targets.

Bioisosteres are often grouped into classical and non-classical types. Classical bioisosteres replace atoms or groups that are closely related in size and electronic character (for example, substituting a carboxylate group with a tetrazole, or exchanging an amide for a similar heteroatom arrangement). Non-classical bioisosteres use different chemotypes to reproduce the same pharmacophoric interactions, sometimes enabling new properties without mirroring the exact functional group. In practice, bioisosterism guides lead modification to improve binding, reduce off-target effects, or enhance oral exposure.

Applications are widespread in drug design, agrochemistry, and related fields. Success depends on empirical validation, since substitutions can alter binding geometry, solubility, and metabolism. Computational modeling, structure-activity relationships, and crystallography often support the selection and evaluation of bioisosteric replacements.

Limitations include that bioisosteric substitutions do not guarantee preserved activity or safety; their effects are context dependent and require experimental testing.