274901-16-5 Usage
Uses
Different sources of media describe the Uses of 274901-16-5 differently. You can refer to the following data:
1. Glyptins are class of oral anti-hyperglycemic agents that inhibit dipeptidyl peptidase 4 (DPP-4), which can act as a serine exopeptidase. Aside from their use in type 2 diabetes, gliptins have positive cardiovascular and anti-inflammtatory effects. Antidiabetic.
2. Vildagliptin (LAF-237) inhibits DPP?4 with IC50 of 2.3 nM
3. The major metabolite of Vildagliptin
Indications and Usage
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.
Mechanisms of Action
Vildagliptin is a selective, competitive and reversible DPP-4 inhibitor. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 21 (GLP21) are important hormones that regulate body glucose concentration and have the same functions as intestinal insulin. Type-2 diabetes patients suffer from GIP insulin secretion failure, so only their GLP21 can promote insulin secretion by affecting receptors on islet beta cell membranes. GLP21 can also inhibit glucagon secretion and inhibit gastric clearing to extend the feeling of fullness (control appetite). DPP-4 binds with proteins in many types of tissues, including tissue in the kidney, liver, small intestine brush border, pancreatic duct, lymph cells, and endothelial cells, and it can deactivate GLP21 by hydrolyzing its N-terminal position-2 alanine. Vildagliptin binds with DPP-4 to produce a DPP-4 compound and inhibit its activity. It increases GLP21 concentration and promotes islet beta cells to produce insulin, while also lowering glucagon concentration, thus lowering blood sugar. Vildagliptin has not noticeable effects on weight.
Adverse reactions
Most common adverse reactions include headache, nasopharyngitis, coughing, constipation, dizziness and excess sweating. There have been very rare cases of hypotension, but it is unclear if conditions are related to this drug. Almost all research shows that the hypoglycemia occurrence rate while using Vildagliptin is similar to the rate when using a placebo. Control trials showed that compared to thiazolidinediones, Vildagliptin causes a similar occurrence rate of headaches, rashes, and other adverse reactions, but Vildagliptin has a lower occurrence rate of adverse reactions forcing patients to cease treatment and of severe adverse reactions.
Description
Vildagliptin, a DPP-4 inhibitor, was launched for the oral treatment of type 2 diabetes. Vildagliptin is the second DPP-4 inhibitor to reach the market behind sitagliptin, which was introduced in 2006. DPP-4 inhibitors act by slowing the inactivation of incretins, which are endogenous peptides involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase the synthesis and release of insulin from pancreatic βcells via intracellular signaling pathways involving cAMP. GLP-1 also lowers glucagon secretion from pancreatic α cells, which leads to reduced hepatic glucose production. However, although GLP-1 and GIP effectively lower blood glucose, they are short-lived as a result of rapid inactivation by the ubiquitous serine protease DPP-4. By inhibiting DPP-4, vildagliptin increases the concentration and duration of active incretin levels, which in turn results in increased insulin release and decreased glucagon levels in a glucose-dependent manner. Both vildagliptin and sitagliptin are potent, competitive, reversible inhibitors of DPP- 4 (IC50=3.5 and 18 nM, respectively), and they both show slow, tight-binding inhibition kinetics.
Chemical Properties
White Solid
Brand name
Galvus
Clinical Use
Dipeptidyl peptidase 4 inhibitor: Treatment of type 2 diabetes mellitus in combination with other antidiabetic drugs
Side effects
The most common adverse events reported in patients receiving vildagliptin included headache, nasopharyngitis, cough, constipation, dizziness, and increased sweating. Vildagliptin is not recommended for patients with liver impairment.
Synthesis
Vildagliptin is chemically derived in three steps starting from L-prolinamide via acylation with chloroacetyl chloride to produce 1-(chloroacetyl)-L-prolinamide, subsequent dehydration of the carboxamide group to the nitrile with trifluoroacetic anhydride, and condensation of the 1-(chloroacetyl)-L-prolinenitrile intermediate with 3-hydroxyadamantan-1-amine.
Drug interactions
Potentially hazardous interactions with other drugs
None known
Metabolism
About 69% of a dose of vildagliptin is metabolised,
mainly by hydrolysis in the kidney to inactive metabolites.
About 85% of a dose is excreted in the urine (23% as
unchanged drug), and 15% in the faeces.
References
1) Balas?et al.?(2007),?The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients;? J. Clin. Endocrinol. Metab.,?92?1249
2) Ahren?et al. (2004),?Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels and reduces glucagon levels in type 2 diabetes;? J. Clin. Endocrinol. Metab., 89?2078
3) Kosaraju?et al. (2013),?Vildagliptin: an anti-diabetes agent ameliorates cognitive deficits and pathology observed in streptozotocin-induced Alzheimer’s disease;? J. Pharm. Pharmacol.,?65?1773
4) Shimizu?et al. (2012),?DPP4 inhibitor vildagliptin preserves? β-cell mass through amelioration of endoplasmic reticulum stress in C/EBPB transgenic mice;? J. Mol. Endocrinol.,?49?125
Check Digit Verification of cas no
The CAS Registry Mumber 274901-16-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,7,4,9,0 and 1 respectively; the second part has 2 digits, 1 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 274901-16:
(8*2)+(7*7)+(6*4)+(5*9)+(4*0)+(3*1)+(2*1)+(1*6)=145
145 % 10 = 5
So 274901-16-5 is a valid CAS Registry Number.
InChI:InChI=1/C18H17F6N3O.H3O4P/c19-13-8-15(21)14(20)6-10(13)5-11(25)7-17(28)26-3-4-27-12(9-26)1-2-16(27)18(22,23)24;1-5(2,3)4/h1-2,6,8,11H,3-5,7,9,25H2;(H3,1,2,3,4)/t11-;/m1./s1
274901-16-5Relevant articles and documents
Continuous preparation method of vildagliptin
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Paragraph 0034-0046, (2021/04/21)
The invention discloses a continuous preparation method of vildagliptin, which comprises the following steps: 1, preparing (S)-1-(2-chloracetyl) pyrrolidine-2-carbonitrile from (S)-pyrrolidine-2-carbonitrile p-toluenesulfonate, chloroacetyl chloride, triethylamine and dichloromethane, washing, separating the liquid, and keeping the organic phase; 2, adding water and 3-amino-1-adamantanol into the organic phase, refluxing, evaporating to remove the organic solvent, heating, and reacting to obtain a feed liquid; 3, washing the feed liquid, cooling, adjusting to be acidic, and washing to obtain feed liquid; and 4, carrying out aqueous phase extraction, cooling, adjusting to alkalinity, carrying out liquid separation to reserve an organic phase, carrying out aqueous phase re-extraction, carrying out liquid separation, merging the organic phases, evaporating to remove the solvent, and adding a crystallization solvent to obtain vildagliptin with HPLC purity of 99.5% or more. The raw material provided by the invention is low in water absorption and convenient to prepare, store and feed; through continuous process operation, the operation steps are reduced, and the overall yield is improved; finally, water is used as a reaction solvent, so that the production cost is reduced, the environmental pollution pressure is reduced, and the method is suitable for preparing vildagliptin.
PROCESS FOR THE PREPARATION OF VILDAGLIPTIN
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Page/Page column 8, (2021/06/22)
The present invention relates to process for the preparation of Vildagliptin. The present invention involves an ecologically friendly process by avoiding the dehydrating agent and use of reagents that are less expensive, easier to handle and its cost effective industrial applicable process.
Cerium-Catalyzed C-H Functionalizations of Alkanes Utilizing Alcohols as Hydrogen Atom Transfer Agents
An, Qing,Chen, Yuegang,Liu, Weimin,Pan, Hui,Wang, Xin,Wang, Ziyu,Zhang, Kaining,Zuo, Zhiwei
, p. 6216 - 6226 (2020/04/27)
Modern photoredox catalysis has traditionally relied upon metal-to-ligand charge-transfer (MLCT) excitation of metal polypyridyl complexes for the utilization of light energy for the activation of organic substrates. Here, we demonstrate the catalytic application of ligand-to-metal charge-transfer (LMCT) excitation of cerium alkoxide complexes for the facile activation of alkanes utilizing abundant and inexpensive cerium trichloride as the catalyst. As demonstrated by cerium-catalyzed C-H amination and the alkylation of hydrocarbons, this reaction manifold has enabled the facile use of abundant alcohols as practical and selective hydrogen atom transfer (HAT) agents via the direct access of energetically challenging alkoxy radicals. Furthermore, the LMCT excitation event has been investigated through a series of spectroscopic experiments, revealing a rapid bond homolysis process and an effective production of alkoxy radicals, collectively ruling out the LMCT/homolysis event as the rate-determining step of this C-H functionalization.