Prodrug design is a strategy to improve the bioavailability of drugs. A prodrug is a pharmacologically inactive compound that is converted into an active drug through chemical or enzymatic processes. Prodrugs can be classified according to their functional groups. Carboxylic acids and alcohols are often converted to ester prodrugs, which are hydrolyzed by esterases to release the active drug. Amines are sometimes converted to amide or Mannich base prodrugs. Azo linkages can be used to link amines, which are released by azo reductase enzymes. Carbonyl groups are occasionally converted to sp3 hybridized derivatives for prodrug design. The earliest example of a prodrug

1. NETES Institute of Pharmaceutical Sciences, Mirza
Presented by-
Jubair Sikdar
Roll no-04
M. Pharm 1st semester
Department of Pharmaceutical Chemistry
PRODRUG DESIGN

2. CONTENTS
 Introduction
 Prodrug of functional group

3. INTRODUCTION
 The term prodrug is defined as a pharmacologically inactive compound that is
converted into an active drug by chemical or enzymatic process. The prodrug
to drug conversion can occur before absorption, during absorption, after
absorption or at a specific site in the body. A prodrug is also called as pro-
agent, bio-reversible derivative, latentiated drug and congeners.
 The earliest example of prodrug is Arshphenamine which is used for the
treatment of syphilis. Later it was found that, the activity of this compound was
due to metabolic Oxophenarsine. Arsphenamine was later replaced by
Oxophenarsine.

4. Prodrugs of functional group
Pro-drugs are also classified according to the functional group. They are
 Carboxylic acids and alcohols
 Amines
 Azo linkages
 Carbonyl compounds
Carboxylic acid and alcohols:
Pro-drugs of carboxylic acid and alcohol functionalities can be prepared by conversion to esters. The
esters can be easily hydrolyzed by esterase enzymes (e.g. lipase, ester hydrolase, cholesterol esterase,
acetyl cholinesterase, and carboxy peptidase) present in plasma and other tissues to give active drug.
Example:

5. Amines:
Due to the high stablility and lack of amidase enzyme necessary for hydrolysis, the conversion of
amines to amide as a pro-drug is not been used for most of the drugs. A more common approach
adopted is to use Mannich bases as pro-drug form of amines.

6. Azo linkage:
Pro-drugs of amines are occasionally prepared by incorporating them in to an azo linkage. By the
action of azo reductase the amino compounds are released in vivo.
• Prontosil drug is inactive in vitro, but it is active in vivo since it is converted to
sulphanilamide by azo reductase enzymes.

7. • Sulphasalazine by the action of azo reductase releases the amino salicylic acid
and sulphapyridine.

8. Carbonyl moiety:
Conversion of carbonyl functionalities, such as aldehyde and ketone, to pro-drug
have not been found wide clinical use. They are converted into derivatives in
which the sp2 carbonyl carbon is converted as sp3 hybridized carbon attached to
hetero-atoms.
For example, hexamine releases formaldehyde in the urine (acidic PH), which
acts as an antibacterial agent.

9. REFERENCES
1. Alagagarsamy V: Text of Medicinal Chemistry, Elsevier, Volume I, 2010:71-81
2. Ilango K & Valentina P: Text Book of Medicinal Chemistry, Keerthi Publication, Volume I,
Second edition, 2015:111-135

10. OPEN TO DISCUSSION

11. THANK YOU