Bioisostere

In medicinal chemistry, bioisosteres are substituents or groups with similar physical or chemical properties that impart similar biological properties to a chemical compound. In drug design, the purpose of exchanging one bioisostere for another is to enhance the desired biological or physical properties of a compound without making significant changes in chemical structure.

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For example, the replacement of a hydrogen atom with a fluorine atom at a site of metabolic oxidation in a drug candidate may prevent such metabolism from taking place. Because the fluorine atom is similar in size to the hydrogen atom the overall topology of the molecule is not significantly affected, leaving the desired biological activity unaffected. However, with a blocked pathway for metabolism, the drug candidate may have a longer half-life.

There are many examples of bioisosteres, which may be equivalent in some instances but not in others depending on what factors are important in binding (electronegativity, size, polarity etc). So for instance a chlorine -Cl group may often be replaced by a trifluoromethyl -CF₃ group, or by a cyano -CN group, but depending on the particular molecule used the substitution may result in little change in activity, or either increase or decrease affinity or efficacy depending on what factors are important for target binding. Another example is aromatic rings, a phenyl -C₆H₅ ring can often be replaced by a different aromatic ring such as thiophene or naphthalene which may either improve efficacy or change specificity of binding.

References

• Annual Reports in Medicinal Chemistry, Vol. 21 (1986), 283-291.

See also

• Isosterism (isostere)
• Grimm's hydride displacement law