Isosteres are atoms, molecules, or ions of similar size containing the same number of atoms and valence electrons. Example 1. Consider neon, the noble gas at the end of the second row of the periodic table. To the left of it, fluorine has one fewer electron.
What is the Grimm concept of Bioisosterism?
Grimm’s Hydride Displacement Law is an early hypothesis to describe bioisosterism, the ability of certain chemical groups to function as or mimic other chemical groups.
What does Isosteres mean?
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.
What is used for Bioisosteric replacement of benzene?
The replacement of para-substituted benzenes with saturated bi- and polycyclic bioisosteres – bicyclo[1.1. 1]pentane, bicyclo[2.2. 2]octane and cubane, – often increases the potency, selectivity and metabolic stability of bioactive compounds.
What is Bioisosteric replacement?
A bioisosteric replacement transforms an active compound into another compound by exchanging a group of atoms with another, broadly similar group of atoms. Several computational methods have been described to automatically identify bioisosteric replacements.
What is isosteres 11?
We can define isostere as the molecules or ions that have a similar shape and often have similar electronic properties.
What is Bioisosterism how is it useful in the design of drug?
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.
What is Isosteres 11?
Why is it important to study medicinal chemistry?
By imparting an exclusive knowledge base, medicinal chemistry plays a vital role in providing critical thinking and evidence-based problem-solving skills to pharmacy students, enabling them to make optimal patient-specific therapeutic decisions.
What is bioisosteric replacement?
What is Bioisosterism give example?
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 improve efficacy, change specificity of binding, or reduce metabolically labile sites on the molecule, resulting in better pharmacokinetic properties.
How does pKa affect drug?
The pKa of a drug is the hydrogen ion concentration (pH) at which 50% of the drug exists in its ionized hydrophilic form (i.e., in equilibrium with its un-ionized lipophilic form). All local anesthetic agents are weak bases. At physiologic pH, the lower the pKa the greater the lipophilicity.
What is bioisostere in pharmacology?
Bioisostere. In medicinal chemistry, bioisosteres are chemical substituents or groups with similar physical or chemical properties which produce broadly similar biological properties to another chemical compound. In drug design, the purpose of exchanging one bioisostere for another is to enhance the desired biological or physical properties…
What is the objective of bioisosteric replacement?
The objective of a bioisosteric replacement is to create a new molecule with similar biological properties to the parent compound. The bioisosteric replacement may be physicochemically or topologically based.
What is the best bioisosteric modification in drug design?
A frequently used bioisosteric modification in drug design is to replace a carboxylic acid group with 1H-tetrazole, as can be seen above both have similar pKa (4.5) and cLogP.
What is the bioisosterism Handbook?
Written with the practicing medicinal chemist in mind, this is the first modern handbook to systematically address the topic of bioisosterism. As such, it provides a ready reference on the principles and methods of bioisosteric replacement as a key tool in preclinical drug development.
