Synthesis Of Hetero-cyclic Drugs

Synthesis of hetero-cyclic drugs like which is under Anti-fungal activities.

1. SYNTHESIS OF HETEROCYCLIC DRUGS Prepared by: Nilam Kaushikbhai Mistry M.Pharm 1 st Sem(Pharmaceutical chemistry) Parul institute of Pharmacy 1

2. CONTENT : Introduction Ketoconazole Terconazole Metronidazole Miconazole 2

3. INTRODUCTION A Heterocyclic compounds are those which has atoms of at least two different elements as members of its ring. Heterocyclic chemistry is a branch of organic chemistry dealing with the synthesis, properties, and applications of these heterocycles. 3

4. KETOCONAZOLE Molecular Formula: C 26 H 28 Cl 2 N 4 O 4 4

5. PROPERTIES Molecular weight : 531.4 g/mol State : solid Color : white crystal or powder Melting point : 146 ̊C Solubility : soluble in organic solvents 5

6. METHOD OF PREPARATION : Take 2-bromo-1-(2,4-dichlorophenyl)ethanone 1 with glycerol 2 was performed to form 3 . Then compound 3 reacts in presence of benzonyl chloride and pyridine(as base) to form 4. Then the 4 react with methanesulfonyl chloride to form 5 , Then 5 was react with 6 and removal of methane sulfonic acid to give KETOCONAZOLE 7 . 6

7. SYNTHESIS : 7

8. 8

9. USES : Orally Effective broad-spectrum antifungal drug. Mucocutaneous candidiasis (immune disorder of T-cell). Used to inhibit excessive production of glucocorticoids in patients with Cushing's syndrome (hypercortisolism). Used to treat fungal infections of the skin such as jock itch, seborrhea, dermatophytosis (ringworm),and mycosis. 9

10. TERCONAZOLE Molecular Formula: C 26 H 31 Cl 2 N 5 O 3 10

11. PROPERTIES Molecular weight : 532.5 g/mol State : solid Color : white powder Melting point : 126.3 ̊C Solubility : insoluble in water & soluble in ethanol 11

12. METHOD OF PREPARATION : STEP:1 Take 1-(2,4-dichlorophenyl)ethanone 1 with glycerine 2 was performed without isolation to form compound 3 . Then 3 treated with benzoyl chloride(BzCl) to benzoylation to form compound 4. Then 4 was reflux with NaOH with the addition of triazole ring to form 5 , Then 5 was coupled with methane sulfonyl chloride(MsCl) to give 6 . 12

13. METHOD OF PREPARATION : STEP:2 Take 1-(4-methoxyphenyl)piperazine 7 treated with isopropyl or methylacetate was performed in presence of HBr to form 8 . Now combine step 1 and step 2 Compound 6 and 8 condensed to form TERCONAZOLE 9 13

14. SYNTHESIS : STEP: 1 14

15. STEP:2 15

16. Condensation of Step:1 & Step:2 16

17. USES : Orally Effective broad-spectrum antifungal drug. Vulvovaginal candidiasis(yeast infection). Effective against dermatomycoses in animal models. Suppository used to treating vaginal yeast infections (Candida). It works by stopping the growth of yeast that caused by fungus. 17

18. METRONIDAZOLE Molecular Formula: C 6 H 9 N 3 O 3 18

19. PROPERTIES Molecular weight : 171.5 g/mol State : solid Color : white or pale yellow crystal Melting point : 160.5 ̊C Solubility : soluble in organic solvents 19

20. METHOD OF PREPARATION : Take ethane-1,2-diamine 1 and cyno methane 2 in presence of zinc powder to form 2-methyl-1H-imidazole 3 . Then 3 reacts in presence of HNO 3 and P 2 O 5 to form 4. Then the 4 was reflux with chloro-ehanone to form METRONIDAZOLE 5 20

21. SYNTHESIS : 21

22. USES : Mainly used as antibiotics knows as nitroimidazoles. Oral tablets used to treat vaginal infections in women. Used to treat G.I tract and reproductive system infections such as amebiasis (intestine infection) and trichomoniasis (sexually transmitted infection). It works by stopping the growth of bacteria and protozoal infection. Used to treat infected insect bites, skin ulcers, bed sores and wounds. 22

23. MICONAZOLE Molecular Formula: C 18 H 14 Cl 4 N 2 O 23

24. PROPERTIES Molecular weight : 416.1 g/mol State : solid Color : white powder Melting point : 161 ̊C Solubility : soluble in organic solvents 24

25. METHOD OF PREPRATION : Take 2-bromo-1-(2,4-dichlorophenyl)ethanone 1 and 1-H imidazole 2 to form compound 3 Then 3 was react with NaBH 4 for reduction of ketone to form 4. Then the 4 was react with 1-(bromomethyl)-2,4-dichlorobenzene to form MICONAZOLE 5 , 25

26. SYNTHESIS : 26

27. USES : Used as a Anti-fungal agents. To treat a skin condition known as pityriasis rosea(skin rash). Works as stop the growth of fungus. Treatment of ringworm including jock itch and athlete’s foot. To treat neonatal oral thrush and vaginal thrush(yeast infection). 27

28. THANK YOU 28