III-PHARM.D, MEDICINAL CHEMISTRY

1. MEDICINALCHEMISTRY
OFHYPOGLYCEMIC
AGENTS
Dr. T.SOUJANYA
PHARM-D

2. HYPOGLYCEMIC AGENTS:-
Hypoglycemic agents are synthetic drugs that lower the
blood glucose levels and are used to treat type-2 diabetes
mellitus.They may stimulate the synthesis of insulin by pancreatic
beta cells,inhibit glucose production,facilitate transport of glucose to
muscle cells and sometimes increase the number of receptor sites
where insulin can be bound and can initiate the process of breaking
down glucose.

3. CLASSIFICATION

4. CLASSIFICATION OF HYPOGLYCEMIC AGENTS:-
1.SULFONYL UREAS:-
I-GENERATION:-
Tolbtamide,Chlorpropamide,Acetohexamide,Tolazamide
II-GENERATION:-
Glibenclamide,Glipizide,Gliclazide,Glimepiride
2.BIGUANIDES:-
Phenformin,Metformin
3.THIAZOLIDINE DIONES:-
Ciglitazone,Troglitazone,Rosiglitazone,Pioglitazone

5. 4.ALPHA GLUCOSIDASE INHIBITORS:-
Acarbose,Miglitol
5.MEGLITINIDES/PHENYL ALANINE ANALOGUES:-
Repaglinide,Nateglinide

6. 1.SULPHONYL UREAS:-
a) Tolbutamide

7. b) Chlorpropamide

8. c)Acetohexamide

9. d)Tolazamide

10. e)Glibenclamide

11. f)Glipizide

12. g)Gliclazide

13. h)Glimepiride

14. 2.BIGUANIDES:-
a)Phenformin b)Metformin

15. 3.THIAZOLIDINE DIONES:-
a)Ciglitazone

16. b)Troglitazone

17. c)Rosiglitazone

18. d)Pioglitazone

19. 4.ALPHA GLUCOSIDASE INHIBITORS:-
a)Acarbose b)Miglitol

20. 5.PHENYL ALANINE ANALOGUES:-
a)Repaglinide b)Nateglinide

21. SYNTHESIS

22. SULFONYL UREAS

23. 1.SYNTHESIS OF TOLBUTAMIDE:-
TolbutamideN-Bu=n-Butane

24. 2.SYNTHESIS OF ACETOHEXAMIDE:-

25. 3.SYNTHESIS OF TOLAZAMIDE:-
Tolazamide
N-aryl sulfonyl
carbamoic ester

26. 4.SYNTHESISOF GLIBENCLAMIDE:-

27. 5.SYNTHESIS OF GLICLAZIDE:-
Gliclazide

28. MOAOF SULFONYLUREAS:-
Sulphonyl ureas stimulate insulin secretion from pancreatic beta
cells without entering the cell.This occurs in the absence of
glucose.Intact pancreatic beta cells are essential for the hypoglycemic
action of sulfonyl ureas.Beta cells contain sulphonyl urea receptors that
appear to be linked to an ATPase-sensitive K+ channel and inhibits the
K+ efflux which leads to depolarisation of the beta cell membrane and
opens voltage-dependant calcium channels.Increased entry of calcium
ions and intracellular binding to calmodulin could activate kinases
involved in exocytosis of secretory granules. Thus more insulin is
released for a given increment of blood glucose.

29. The order of potency of sulfonyl urea in binding to beta
cells approximates its potency in stimulating the release of insulin and
inhibiting the effect of K+.In addition,sulfonyl ureas appear to act
synergistically with insulin possibly by increasing insulin sensitivity at a
post-receptor level.

31. BIGUANIDES

32. SYNTHESIS OF METFORMIN:-
Dimethyl amine
Dicyandimide
Metformin

34. THIAZOLIDINE DIONES

35. SYNTHESISOF CIGLITAZONE:-
Ciglitazone

36. MOAOF THIAZOLIDINEDIONES:-
Ciglitazone,a thiazolidine-2,4 dione,is a potent hypoglycemic
agent in obese diabetic patients and not in normal or insulin deficient
animals.The mechanism of action of thiazolidine diones is not
understood.Because they require the presence of insulin to show
activity in vivo and appear to enhance insulin action in the hormone
target tissues (eg:-liver,muscle,fat) they are known as insulin
sensitizers.