Prodrug.pptx

M.Pharm
Department of Pharmaceutical Chemistry

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