Isoteres

Isoteres:
Classical Isosteres are molecules or ions with similar shape and often electronic properties.
Many definitions are available. but the term is usually employed in the context of bioactivity
and drug development. Such biologically-active compounds containing an isostere is called
a bioisostere. This is frequently used in drug design the bioisostere will still be recognized and
accepted by the body, but its functions there will be altered as compared to the parent
molecule.
Non-classical isosteres do not obey the above classifications, but they still produce similar
biological effects in vivo. Non-classical isosteres may be made up of similar atoms, but their
structures do not follow an easily definable set of rules.
The isostere concept was formulated by Irving Langmuir in 1919, and later modified by
Grimm. Hans Erlenmeyer extended the concept to biological systems in 1932. Classical isosteres
are defined as being atoms, ions and molecules that had identical outer shells of electrons, This
definition has now been broadened to include groups that produce compounds that can
sometimes have similar biological activities. Some evidence for the validity of this notion was
the observation that some pairs, such as benzene, thiophene, furan, and even pyridine,
exhibited similarities in many physical and chemical propertiesiea
Bioisoteres
In medicinal chemistry, bioisosteres are chemical substituents or groups with similar physical
or chemical properties which produce broadly similar biological properties in the same 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. The main use of this term and its techniques are related to
pharmaceutical sciences. Bioisosterism is used to reduce toxicity, change bioavailability, or
modify the activity of the lead compound, and may alter the metabolism of the lead.
Classical bioisosteres
Classical bioisosterism was originally formulated by James Moir and refined by Irving
Langmuir as a response to the observation that different atoms with the same valence
electron structure had similar biological properties.
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.
 Procainamide, an amide, has a longer duration of action than Procaine, an ester, because of
the isosteric replacement of the ester oxygen with a nitrogen atom. Procainamide is a
classical bioisostere because the valence electron structure of a disubstituted oxygen atom
is the same as a trisubstituted nitrogen atom, as Langmuir showed.
Another example is seen in a series of anti-bacterial chalcones. By modifying certain
substituents, the pharmacological activity of the chalcone and its toxicity are also modified.
Non-classical bioisosteres
Non-classical bioisosteres may differ in a multitude of ways from classical bioisosteres, but
retain the focus on providing similar sterics and electronic profile to the original functional
group. Whereas classical bioisosteres commonly conserve much of the same structural
properties, nonclassical bioisosteres are much more dependent on the specific binding needs of
the ligand in question and may substitute a linear functional group for a cyclic moiety, an alkyl
group for a complex heteroatom moiety, or other changes that go far beyond a simple atom-
for-atom switch.
For example, a chloride -Cl group may often be replaced by a trifluoromethyl -CF 3 group or by a
cyano -C≡N group. Depending on the particular molecule used, the substitution may result in
little change in activity, or either increased or decreased affinity or efficacy - depending on what
factors are important for ligand binding to the target protein. Another example is aromatic
rings, where a phenyl -C6H5 ring can often be replaced by a different aromatic ring such
as thiophene or naphthalene which may improve efficacy, change specificity of binding or
reduce metabolically labile sites on the molecule, resulting in better pharmacokinetic
properties.
 Alloxanthine is an inhibitor of xanthine oxidase. It is also an isostere of xanthine, the normal

substrate for the enzyme. Alloxanthine is considered a non-classical bioisostere because of
the scaffold change.
Silafluofen is an isostere of pyrethroid insecticides.
 Silafluofen is an organosilicon analogue of pyrethroid insecticide Etofenprox, wherein a

carbon center has been replaced by isosteric silicon, and in addition, one hydrogen
atom is replaced by isosteric fluorine

Isoteres

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Isoteres:

 Alloxanthine is an inhibitor of xanthine oxidase. It is also an isostere of xanthine, the normal

Silafluofen is an isostere of pyrethroid insecticides.

 Silafluofen is an organosilicon analogue of pyrethroid insecticide Etofenprox, wherein a

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