|Vildagliptin Chemical Properties|
|Vildagliptin Usage And Synthesis|
|Treatment of type 2 diabetes drugs||Vildagliptin (vildagliptin), developed by Novartis (Novartis) Pharmaceutical Co., Ltd, is another oral administrated inhibitor of Dipeptidyl peptidase-IV after sitagliptin (sitagliptin). In 2008, it is approved for marketing in the European Union for the treatment of type 2 diabetes.|
Diabetes is a chronic metabolic disease with its prevalence being increased year by year. Type 2 diabetes is a complicated diseases caused with the combined action between polygenic genetic factors and environmental factors.
Dipeptidyl peptidase IV (DPP-IV) inhibitors are a new class of anti-diabetic drugs which induces and facilitate the biosynthesis and secretion of insulin. It plays a role in lowering the blood carbohydrate concentration through multiple mechanisms such as inhibiting the β cell apoptosis, inhibiting glucagon secretion and reducing food intake. During its lowering effect on reducing blood carbohydrate levels, it can also reverse the situation of deteriorating function of pancreas islet for diabetic patients at the same time. Vildagliptin is the representative of drugs among the dipeptidyl peptidase inhibitor. It exhibited a good anti-diabetic effects and tolerance no matter whether it is being administered alone or in combination with metformin and insulin medication in clinical studies.
|Pharmacological effects||Vildagliptin is a selective, competitive and reversible inhibitor of DPP24. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 21 (GLP21) are both essential hormones in maintaining the in vivo glucose concentrations which both have incretin effect. Insulin secretion effect of GIP in patients of type 2 diabetes GIP is destroyed with only GLP21 plays a function of insulinotropin secretion. GLP21 promotes the secretion of insulin by acting on pancreatic β cell membrane receptors. GLP21 can also inhibit the glucagon secretion and inhibit the gastric emptying thereby increasing satiety (appetite suppressant). DPP24 binds to protein and is presented in many tissues, such as brush-like kidney, liver, small intestine edges of the membrane, the pancreatic duct cells, and endothelial cells. DPP24 can rapidly deactivate GLP21 by hydrolysis the first two N-terminal alanine of GLP21. This product can form complex with DPP24 to inhibit the enzyme activity. At the same time of improving concentration of GLP21 and promoting pancreatic β cells to produce insulin, it reduces the glucagon concentrations, thereby reducing blood sugar with no significant effect on body weight.
|Production method||L-proline has its amino group protected by di-tert-butyl dicarbonate ester, and further goes through carbonylamino reaction together with ammonia at the presence of 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide (EDC). Then remove the Boc protecting group with hydrochloric acid to obtain L-prolinamide (intermediate 4), L-prolinamide is further acylated by chloroacetyl chloride to obtain (S)-N-chloroacetyl-2-carbamoyl-pyrrolidin alkoxy (intermediate 2); dehydrate to obtain (S)-N-chloroacetyl-2-cyano pyrrolidine (intermediate 3), and finally have nucleophilic reaction with 3-amino-1-adamantanol (4) to obtain vildagliptin.|
Figure 1 L-prolinamide prepared vildagliptin chemical reaction scheme
The above information is edited by the Chemicalbook of Dai Xiongfeng.
|Side effects||1. The most common adverse reactions include headache, nasopharyngitis, cough, constipation, dizziness and sweating. Very small number of patients got hypertension medication symptoms, but the correlation with the drug is still not clear. Almost all of the research results have confirmed that the use of incidence of hypoglycemia upon using vildagliptin is approximate to that upon using placebo.|
2. Control trial has found that compared with thiazolidinediones, the incidence of adverse reactions in patients such as headache, rash is similar while using vildagliptin. However, the incidence of stopping drug due to adverse reactions or severe adverse reactions is the lowest when using vildagliptin.
|Chemical Properties||White Solid|
|Usage||Vildagliptin (LAF-237) inhibits DPP?4 with IC50 of 2.3 nM|
|Usage||The major metabolite of Vildagliptin|
|Usage||Labelled Vildagliptin. It is a new oral anti-hyperglycemic agent of a new dipeptidyl peptidase-IV (DPP-IV) inhibitor class of drugs. Antidiabetic.|
|Usage||A metabolite of Vildagliptin|
|Vildagliptin Preparation Products And Raw materials|