The document discusses bioisosterism, defined as the replacement or modification of functional groups by similar substitutes to enhance selectivity and reduce toxicity in pharmacology. It classifies bioisosteres into classical and non-classical types, providing examples and highlighting their utility in improving drug properties. Changes due to bioisosteric replacement include structural alterations and effects on receptor interactions and pharmacokinetics.

1. BIOISOSTERISM
Submitted by
R. ANBARASAN
2ND M.Sc BIOTECHNOLOGY
ANNAMALAI UNIVERSITY

2. CONTENT
 Introduction
 Isometric replacement
 Utilization
 Classification
 Changes occur
 Reference

3. INTRODUCTION
 ISOSTERISM
Langmuir in 1919- compounds or group of
atoms with same number of atoms and
electrons
Eg., Co2, - O=C=O
N2O –N=N+=O

4.  BIOISOSTERES- Burger defines, “substitute or groups
with chemical or physical similarities
 Produce similar biological properties
 Replacement or modification of functional group with
other having similar properties called bioisosteric
replacement

5. Why isosteric replacement?
 Greater selectivity
 Less side effects
 Deceased toxicity
 Improved pharmacokinetics
 Increase stability

6. UTILITY OF BIOISOSTERES
 Improving potency
 Enhancing selectivity
 Altering physical properties
 Reducing or redirecting metabolism
 Eliminating or modifying toxicophores
 Acquiring novel intellectual property

7. CLASSIFICATION
 Classified into two types:
Classical bioisosteres
Non classical bioisosteres

8.  Classical bioisosteres are further classified:
 Univalent atoms and groups (C, N, O, S, -Cl, -Br)
 Bivalent atoms and groups (R-O-R, R-S-R, R-NH-R)
 Trivalent atoms and groups (-CH=, -N=, R-N=R)
 Tetravalent atoms and groups (=C=, =N=, =P=)
 Ring equivalent

9.  Non – classical bioisosteres don’t have same number
of atoms
 It don’t fit for steric and electronic rules
 But produce similar biological activity
a) Halogens (Cl, F, Br)
b) Ethers (-R-O-R, -S-)
c) Hydroxy groups (-OH)
d) Carboxylic acid group (-R-COOH, R-SOOH)
e) Catechol

10. CHANGES OCCUR:
 Some changes resulting from bioisosteric replacement
1. Structural (size, shape, H-bonding)
2. Receptor interactions (lipid or water solubility)
3. Pharmacokinetics (lipophilicity, hydrophilicity, Pka, H-
bonding)

11.  For example;
Cyclopropyl group used as bioisosteric for an alkaline
group in prodrugs and opioid antagonists
Replacing a functional group, important for target binding,
but problematic on one way or other
For example, thiourea group was present as important
binding group in early histamine antagonist but was
responsible for toxic side effects
replacing it with bioisosteric allow binding without
toxicity

13. REFERENCE
 Prof. S.V. Amrutkar slideshare in SCRIBD
 www.tubakhanslideshare//slideshare.com
 Graham L.Patrick book An introduction to medical
chemistry