Antidiabetic agents-medicinal chemistry

Insulin and its preparations
Sulfonyl ureas: Tolbutamide*, Chlorpropamide, Glipizide, Glimepiride, Glibenclamide.
Biguanides: Metformin.
Thiazolidinediones: Pioglitazone, Rosiglitazone. Meglitinides: Repaglinide, Nateglinide.
Glucosidase inhibitors: Acrabose, Voglibose

1. Anti diabetic agents SUBJECT:- MEDICINAL CHEMISTRY-II B.PHARMACY SEMSTER:- V SEM PREPARED BY Dr.D Mahendra,M.Pharm,PharmD-PB,(MBA)(Ph.D),. Research Scholar at parul University Asst Professor-Nova College of Pharmacy

2. CHEMISCAL CLASSIFICATION OF ANTI DIABEBETIC AGENTS Sulfonyl ureas: Tolbutamide*, Chlorpropamide, Glipizide, Glimepiride, Glibenclamide. Biguanides: Metformin. Thiazolidinediones: Pioglitazone, Rosiglitazone. Meglitinides: Repaglinide, Nateglinide. Glucosidase inhibitors: Acrabose, Voglibose.

3. SULFONYL UREAS Tolbutamide:- The synthesis of tolbutamide involves addition reaction of p-toluene sulfonamide and butyl isocyanate in the presence of triethylamine and tetrahydrofuran .

4. SAR OF SULPHONYLUREAS 1.The benzene ring should contain a substitutent preferably in the para position. The substituents , such as methyl, acetyl, amino, chloro , bromo , trifluoro methyl, and dithiomethyl were found to enhance the antihyperglycaemic activity. 2. When the para position of benzene is substituted with aryl carboxamidoalkyl group (second-generation sulphonylureas , such as glibenclamide ) the activity was found to be enhanced further.

5. 3. The size of the group attached to the terminal nitrogen is crucial for activity. The group should also impart lipophilicity to the compound  N -methyl and ethyl substituents that show no activity, whereas  N - propyl and higher homologues were found to be active and the activity is lost when the  N -substituent contains 12 or more carbons.

6. CHLORPROPAMIDE-STRUCTURE & USES Chlorpropamide is an oral anti-hyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It belongs to the sulfonylurea class of insulin secretagogues which act by stimulating β cells of the pancreas to release insulin.

7. GLIPIZIDE -STRUCTURE & USES Glipizide is used to treat high blood sugar levels caused by a type of diabetes mellitus (sugar diabetes) called type 2 diabetes. In type 2 diabetes, your body does not work properly to store excess sugar and the sugar remains in your bloodstream

8. GLIMEPIRIDE -STRUCTURE & USES Glimepiride is used to treat high blood sugar levels caused by type 2 diabetes. It may be used alone, or in combination with insulin or another oral medicine such as metformin . In type 2 diabetes, insulin produced by the pancreas is not able to get sugar into the cells of the body where it can work properly.

9. GLIBENCLAMIDE -STRUCTURE & USES Glibenclamide is used to lower the blood sugar level in patients with type 2 diabetes mellitus that is not controlled by diet and exercise alone. . It is used along with diet and exercise to improve blood sugar control in adults with type 2 diabetes. Glibenclamide is an antidiabetic medication

10. BIGUANIDES Metformin:- M.O.A:- Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.

11. USES OF METFORMIN

12. THIAZOLIDINEDIONES M.O.A:- TZDs reduce insulin resistance in adipose tissue, muscle and the liver. However, PPAR gamma is predominantly expressed in adipose tissue. It is possible that the effect of TZDs on insulin resistance in muscle and liver is promoted via endocrine signalling from adipocytes . Pioglitazone:-

13. PIOGLITAZONE USES Pioglitazone  is a  diabetes  drug ( thiazolidinedione -type, also called " glitazones ") used along with a proper  diet and exercise  program to control high  blood sugar  in patients with  type 2 diabetes . It works by helping to restore your body's proper response to  insulin , thereby lowering your  blood sugar .Controlling high  blood  sugar helps prevent  kidney  damage, blindness, nerve problems, loss of limbs, and sexual function problems. Proper control of diabetes may also lessen your risk of a  heart attack  or  stroke .

14. ROSIGLITAZONE-STRUCTURE & USES Rosiglitazone is used to treat a type of diabetes mellitus called type 2 diabetes. It may be used alone or with other medicines such as Metformin or sulfonylurea agents. Rosiglitazone is used together with a proper diet and exercise to help control blood sugar levels.

15. Meglitinides Mechanism of action:- Meglitinides ( glinides ) are based on the sulfonylurea moiety of glibenclamide (called meglitinide ). They bind to the SUR1 receptor on the β-cell, although with lower affinity than sulfonylureas , and stimulate insulin release in the same way. USES:- Repaglinide is used together with diet and exercise to treat high blood sugar (glucose) levels in patients with type 2 diabetes. Repaglinide works by causing your pancreas to release more insulin into the blood stream. This medicine does not help patients who have insulin-dependent or type 1 diabetes.

16. Nateglinide Nateglinide is used together with diet and exercise to control blood sugar levels in patients with type 2 diabetes. It works by causing your pancreas to release more insulin into the blood stream. This medicine does not help patients who have insulin-dependent or type 1 diabetes.

17. Glucosidase inhibitors Mechanism of ActionAlpha-glucosidase inhibitors inhibit the absorption of carbohydrates from the small intestine. They competitively inhibit enzymes that convert complex non-absorbable carbohydrates into simple absorbable carbohydrates. These enzymes include glucoamylase , sucrase , maltase, and isomaltase .

18. Acarbose is used  to treat type 2 diabetes. Normally, your pancreas releases insulin into the blood stream after you eat. Insulin is used by all the cells in your body to help turn the food you eat into energy. This is done by using glucose (sugar) in the blood as quick energy. Voglibose :- Voglibose is an alpha- glucosidase inhibitor that is used to treat diabetes mellitus by lowering post- prandial blood glucose levels. It helps to delay the absorption of sugar in the body and thereby it reduces the macrovascular complication risks.

19. THANK YOU