Once a lead compound or a pharmacophore structure with the desired pharmacological effect has been identified, organic chemists can introduce modifications in the chemical structure of the lead compound with the goal of improving the pharmacokinetics or pharmacodynamics of a drug candidate. These evolved structures are known as analogs. 3

1. TUMKUR UNIVERSITY
Department Of Studies And Research In Organic Chemistry
Seminar Presented On,
"FUNCTIONAL GROUP MODIFICATION : Medicinal
Chemistry"
Under the Guidance
Pavan Kumar. K
DOSR In Organic Chemistry
Tumkur University, Tumakuru.
Presented by
MANASA .A
Register Number : P11AZ22S104050
1st Year M.Sc., 1st Semester.
2022-2023
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2. CONTENTS
Introduction
Functional group modification
Role of pharmocophores in functional group
Role of a functional group "Pharamacophores" in Receptor binding
of drugs
Role of functional groups in absorption and biovailiabilty
Conclusion
Reference
2

3. INTRODUCTION
Once a lead compound or a pharmacophore structure with
the desired pharmacological effect has been identified,
organic chemists can introduce modifications in the chemical
structure of the lead compound with the goal of improving
the pharmacokinetics or pharmacodynamics of a drug
candidate. These evolved structures are known as analogs.
3

4. 4

5.  The amino group of carbutamide was replaced by a methyl group
to give to Tolbutamide (R=CH3 : arinase) and in so doing the
antibacterial activity was seperated away from the antidiabetic
activities.
 The antibacterial agent, carbutamide side effect: however it could
be not be used as an antidiabetic drug because of its antibacterial
activity which could lead to bacterial resistance.
 In some cases , an experienced medical chemist knows that the
functional group will elicit a particular effect chlorothiazide (Aldo)
5

6. Tolbutamide (R=CH3) (antidiabatic)
Chlorothiazide Diazoxide 6
Carbutamide (antibacterial and
antidiabatic)

7. Consequently diazoxide (Hypeurtat) was prepared as an anti-hypertensive
drug without diuretic activity.
Obviously there is a relationship between the molecular structure of a
compound and its activity.
This phenomenon was first realized about 145 years ago.
In the above example removal of the sulfonamides side chain in chlothiazide
helped to design Diazoxide an anti-hypertensive agent without diuretic effect.
The replacement of amino group of carbutamide (antibacterial) was replaced
by methyl group to give tolbutamide(anti-diabetic agent)
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8. Role of Pharmacophores in Functional group
For a given drug molecule functional groups play a significant role in the:
Overall water / lipid solubility.
Route of administration.
Ability to interact with specific biological targets.
Mechanism of action.
Route of metabolism and elimination.
Duration of action.
Suitability for a specific therapeutic situation.
Tendency to cause adverse effects or drug interactions.
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9. Functional Group A : Provided ionic bond that allows this drug to interact
with its target enzyme.
Functional Group B : Interact with a zinc atom involved in normal substrate
catalysis.
Functional Group C : interact with a hydrophobic site and greatly enhance
binding.
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Role of Functional group "Pharmacophores" in Receptor Binding of Drugs
Functional Group C
Functional Group B
Functional Group A
Enalaprilat

10. Role of Functional groups " Pharmacophores" in Absorption and
Bioavailability.
The addition of methyl group can sterically block metabolism and thus
increase the duration of action of a specific drug molecule.
This was described previously in the addition of the methyl group to . An
additional example of this concept is demonstrated when comparing
testosterone with methyltestosterone.
10

11. Testosterone is a naturally occurring androgenic hormone however, it
cannot be taken orally due to rapid oxidation of the C17 hydroxyl group to
an inactive ketone.
Addition of a methyl group at the C17 position converts the secondary
hydroxyl group into tertiary hydroxyl group. this blocks oxidative metabolism
and methyltestosterone to be administered orally.
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12. The concept of functional groups (FGs), sets of connected atoms that can
determine the intrinsic reactivity of the parent molecule and in part are
responsible for the overall properties of the molecule, form a foundation
within modern medicinal chemistry.
Each functional group has an solubility effect, and a steric effect that needs
to be considered when evaluating the overall
pharmacodynamic and pharmacokinetic properties of any given drug
molecule.
A reaction in which functional group undergoes a change that does not
affect the number of atoms in the skeleton of the molecule.
Conclusion

13. Reference
Text book of medicinal chemistry - Volume-11. (Page number
390)
- K Ilango, P Valentina.
The organic chemistry of Drug design and drug action.
(Page number -57)
-Richard B Silvermann and Mark W Holladay.
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