Synthesis of Advance Organic Chemistry and Medicinal Chemistry Used for Antifungal Drug

1. Advance Organic Chemistry-1
Guided by Prepared by
Mr. Atul Hemke Ms. Puja Basule
M- Pharm First Year (1st sem)
Topic – Ketoconazole, Metronidazole, Terconazole &
Miconazole Synthesis
Department of P’ceutical Chemistry SKB College of
Pharmacy
1

2. Contents
• Metronidazole Introduction
Synthesis
Mechanism
Properties & Uses
 Ketoconazole & Terconazole Introduction
Synthesis
Mechanism
Properties & Uses
• Miconazole Introduction
Synthesis
Mechanism
Properties & uses
2

3. Metronidazole
• Metronidazole is a synthetic nitroimidazole antibiotic that
acts againts anaerobic bacteria & some protozoa
• Antiprotozoal & Antibacterial Activity
• Metronidazole has a broad spectrum activity. It acts againts
anaerobic bacteria and some protozoa as Amoeba & Giardia
IUPAC Name:- 2-(2-Methyl-5-Nitro-1-yl)ethanol
Molecular Formula:- C6H9N3O3
Molar Mass:- 171.156 g/mol-1
Melting Point:- 159 to 163OC
3

4. 4

5. Mechanism of Action
• Metronidazole (prodrug)
enter
• Aerobic & Anaerobic Bacteria
(micro-organism)
• Reduced to 5-nitro position
(ferred oxins)
• Produces number of short lived cytotoxic intermediates
• Cytotoxic products react with DNA & other macromolecules
(damage microbial DNA)
• Cell Death
5

6. Properties
• It is a white or crystalline powder
• Slightly soluble in water, acetone, alcohol &
methylene chloride.
Uses
• It is used in the treatment of intestinal & hepatic
amoebiasis.
6

7. Ketoconazole
• Ketoconazole belongs to the class of drug called Azole
antifungal.
• It work by stopping the growth of the fungus.
• Ketoconazole should not be used to treat fungal infections on
the skin and nails due to the risk of serious side effects & drug
interaction.
• IUPAC Name:- 1-[4-[4-[[2-
2,4-dichlorophenyl)-2-(imida
zole -1-ylmethyl)-1,3-dioxola
n-4-yl]methoxy]phenyl]piper
azin-1-yl]ethanone
• Molar mass:- 531.4g/mol
• Formula:-C26H28CL2N4O4
7

8. Synthesis of Ketoconazole
8

9. Mechanism of Action
• Inhibits an enzyme, resulting in cell wall leaking
• Block demethylation of lanosterol to ergosterol
• Leads to altered cell membrane (unstable)
• Fungal cell death
9

10. Properties
• ketonazole is a white powder
• Pratically insoluble in water
• Soluble in methylene chloride & in methanole
• Sparingly soluble in alcohol
Uses:-
• It is used as antifungal agent
10

11. Miconazole
• Meconazole is an antifungal
synthetic derivative of Imidazole
& use in the tratment of candidal
Skin infection
IUPAC Name:- 1-(2,4-dichlorophenyl)-
2-(imidazole-1-yl)ethanol
Molecular Formula:- C18H14CL4N2O
Molecular wt:- 461.1 g/mol
Melting point:- 159-1630C
11

12. Synthesis of Miconazole
12

13. Mode of action
• Inhibit an enzyme, resulting in cell membrane leaking
• Lead to altered cell membrane
• Finally fungal cell death
13

14. Properties
• It is a white powder
• Very slightly soluble in water & slightly soluble in alcohol
• Sparingly soluble in methanol
Uses:-
• It is used as an Antifungal agent
14

15. Reference
1. Text book of ‘Medicinal Chemistry’ “V.Alagarsamy” Third
edition volume- 1 & 2
2. Text book of ‘Pharmacology’ “Triphati” sixth edition
15

16. 16