(2S)-1-(Chloroacetyl)-2-pyrrolidine carbonitrile 207557-35-5

(2S)-1-(Chloroacetyl)-2-pyrrolidine carbonitrile is an intermediate of Vildagliptin The chemical formula of vildagliptin compound is (-) - (2S) -1- [[(3-hydroxytricyclic [3.3.1.1 [3,7]] silane 1-yl) amino] acetyl] pyrrolidine 2-carboxonitrile. The clinical drug is another dipeptidyl peptidase IV (DPP-IV) inhibitor administered orally after sitagliptin. It was approved by Novartis Pharmaceutical Co., Ltd. of Switzerland to be listed in the European Union in 2008 for the treatment of type 2 diabetes.

Vigagliptin is a selective, competitive, and reversible DPP24 inhibitor. Glucose dependent insulinotropic peptide (GIP) and glucagon like peptide-1 (GLP-1) are important hormones that maintain glucose concentration in the body, both of which have intestinal proinsulin effects. In patients with type 2 diabetes, GIP has impaired insulin secretion. Only GLP-1 can promote insulin secretion by acting on the receptor on the pancreatic beta cell membrane. GLP-1 can also inhibit the secretion of glucagon and inhibit gastric emptying, thereby increasing satiety (inhibiting appetite). DPP24 binds to proteins in many tissues, such as the brush like edges of the kidney, liver, and small intestine membranes, pancreatic ducts, lymphocytes, and endothelial cells. It can quickly inactivate GLP-1 by hydrolyzing its N-terminal second alanine. This product inhibits the activity of the enzyme by combining with DPP24 to form a DPP24 complex. It increases the concentration of GLP-1, promotes insulin production by pancreatic beta cells, and reduces the concentration of glucagon, thereby lowering blood sugar. And it has no significant impact on weight.

Pharmacokinetic studies on healthy individuals have shown that this product is rapidly absorbed after oral administration, with an absorption rate of 85%, a protein binding rate of 4% to 17%, and a Tmax of 1-2 hours. When the dosage is between 25-200mg, there is a linear relationship between blood drug concentration and dosage, with t1/2 ranging from 1.5-4.5 hours. When administered at a single dose of 25-200 mg, the inhibition rate of DPP-IV in plasma can reach over 90% within 30-60 minutes, but the duration of inhibition depends on the dose. When the dose is 50 and 100 mg, the 12 hour inhibition rates of DPP-IV are 70% and 90%, respectively, while the 24-hour inhibition rate of DPP-IV in the 100 mg group is 40%. This product is mainly metabolized through hydrolysis of cyanide groups (55%). In addition, 22% of drugs are excreted through the kidneys as prototype drugs, and a very small portion of drugs are metabolized through cytochrome P450 enzymes. However, this product is neither an inhibitor nor an inducer of this enzyme. There was no drug accumulation during multi dose administration, and patients with liver and kidney dysfunction did not need to adjust the dosage. The pharmacokinetic results were also not affected by food.