Sitagliptin

Base Information

• Chemical Name: Sitagliptin
• CAS No.: 486460-32-6
• Molecular Formula: C16H15F6N5O
• Molecular Weight: 407.318
• European Community (EC) Number: 690-730-1
• UNII: QFP0P1DV7Z
• DSSTox Substance ID: DTXSID70197572
• Nikkaji Number: J2.231.708C
• Wikipedia: Sitagliptin
• Wikidata: Q419832
• NCI Thesaurus Code: C73838
• RXCUI: 593411
• Pharos Ligand ID: 1CS459QWD6NB
• Metabolomics Workbench ID: 43467
• ChEMBL ID: CHEMBL1422
• Mol file: 486460-32-6.mol

Synonyms:0431, MK;4-oxo-4-(3-(trifluoromethyl)-5,6-dihydro(1,2,4)triazolo(4,3-a)pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-2-amine;Anhydrous, Sitagliptin Phosphate;Januvia;MK 0431;MK-0431;MK0431;Monohydrate, Sitagliptin Monophosphate;Monohydrate, Sitagliptin Phosphate;Monophosphate Monohydrate, Sitagliptin;Phosphate Anhydrous, Sitagliptin;Phosphate Monohydrate, Sitagliptin;Phosphate, Sitagliptin;sitagliptin;sitagliptin monophosphate monohydrate;sitagliptin phosphate;sitagliptin phosphate anhydrous;sitagliptin phosphate monohydrate

Chemical Property of Sitagliptin

Chemical Property:

• Appearance/Colour: yellow grease
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 114.1-115.7 °C
• Refractive Index: 1.59
• Boiling Point: 529.9 °C at 760 mmHg
• PKA: 7.20±0.10(Predicted)
• Flash Point: 274.3 °C
• PSA: 77.04000
• Density: 1.61 g/cm³
• LogP: 2.65470
• XLogP3: 0.7
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 10
• Rotatable Bond Count: 4
• Exact Mass: 407.11807909
• Heavy Atom Count: 28
• Complexity: 566

Purity/Quality:

99.5%, ^*data from raw suppliers

Sitagliptin ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antidiabetic Agents
• Canonical SMILES: C1CN2C(=NN=C2C(F)(F)F)CN1C(=O)CC(CC3=CC(=C(C=C3F)F)F)N
• Isomeric SMILES: C1CN2C(=NN=C2C(F)(F)F)CN1C(=O)C[C@@H](CC3=CC(=C(C=C3F)F)F)N
• Recent ClinicalTrials: Perioperative Sitagliptin Medication for Reduction of the Inflammatory Response Associated With Cardiopulmonary Bypass
• Recent EU Clinical Trials: Efficacy of metformin versus sitagliptin on benign thyroid nodules size in type 2 diabetes: a 2-years prospective multicentric study
• Recent NIPH Clinical Trials: Effect of omarigliptin on glucose variability and oxidative stress in type 2 diabetes patients
• Description: Sitagliptin is an orally-bioavailable selective DPP4 inhibitor that was discovered through the optimization of a class of β-aminoacid-derived DPP4 inhibitors. It lowers DPP4 activity in a sustained manner following once daily administration, preserves the circulating levels of intact GIP and GLP1 following meals in both acute and chronic studies and reduces blood glucose levels without significant increases in hypoglycaemia. Sitagliptin phosphate (STG) is used to treat DM type 2 because it improves glycemic control by increasing the levels of active incretin hormones, GLP-1 (peptide-1) and GIP (glucose-dependent insulinotropic peptide). The activation of these incretins in β-pancreatic cells causes increased levels of cyclic adenosine monophosphate (cAMP) and intracellular calcium, with subsequent glucose-dependent insulin secretion (2). This hypoglycemic drug belongs to a new class called dipeptidyl peptidase IV inhibitors. STG was approved by the FDA in 2006. Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is a first-in-class oral drug launched for the treatment of type 2 diabetes. It acts by slowing the inactivation of incretins, which are endogenous peptides involved in the physiologic regulation of glucose homeostasis. Incretin hormones, including glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. When blood glucose concentrations are normal or elevated,GLP-1 and GIP increase the synthesis and release of insulin from pancreatic b cells via intracellular signaling pathways involving cAMP. GLP-1 also lowers glucagon secretion from pancreatic αcells, which leads to reduced hepatic glucose production.
• Indications: Sitagliptin is approved by the FDA as an adjunct to diet and exercise to improve glycaemic control in patients with T2DM, either as a monotherapy, or in combination with metformin or a peroxisome proliferatoractivated receptor-γ agonist (for example, thiazolidinediones) when the single agent does not provide adequate glycaemic control.
• Clinical Use: In October 2006, the U.S. Food and Drug Administration (FDA) approved sitagliptin as monotherapy and as add-on therapy to either of two other types of oral diabetes medications, metformin or thiazolidinediones to improve blood glucose control in patients with type 2 diabetes when diet and exercise are not enough. In March, 2007 it was approved in European Union. Sitagliptin is currently approved in 42 countries. The recommended dose of sitagliptin is 100 mg once daily. It may be taken with or without food. In April, 2007 FDA approved the combination product of sitaglibtin and metformin for type 2 diabetes. In clinical trials of 1-year duration, sitagliptin improved glycaemic control by reducing both fasting and postprandial glucose concentrations, leading to clinically meaningful reductions in glycosylated haemoglobin levels. Monotherapy with sitagliptin 100mg daily decreases mean HbA1c by 0.6- 0.79% (mean difference from placebo). When used in combination with metformin or pioglitazone, the mean reduction is HbA1c is 0.7% and 0.9% respectively. Sitagliptin is considered to be weight neutral and lipid neutral. Treatment of type 2 diabetes in combination with metformin or a thiazolidinedione
• Drug interactions: Sitagliptin plasma concentrations may be increased modestly (approximately 68%), with cyclosporine which is not expected to be clinically important. Digoxin plasma levels may be increased slightly (approximately 18%), no dosage adjustment is recommended. Although sitagliptin is not as likely to cause hypoglycemia as some other oral diabetes medications, be careful while prescribing any other drug that can potentially lower blood sugar, such as: probenecid, nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin or other salicylates, sulfa drugs, a monoamine oxidase inhibitor (MAOI) or beta-blockers. Potentially hazardous interactions with other drugs None known
• Uses: Sitagliptin is a useful pharmaceutical drug. Could be useful for treating intestinal inflammation, diabetes, pre-?diabetes, impaired glucose tolerance, hepatitis, and?/or inflammatory liver disease. Labeled Sitagliptin , intended for use as an internal standard for the quantification of Sitagliptin by GC- or LC-mass spectrometry.

Technology Process of Sitagliptin

There total 211 articles about Sitagliptin which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 96.7%

C23H21F6N5O (1306610-49-0) → sitagliptin (486460-32-6,823817-55-6)

Guidance literature:

With Pt/Al₂O₃; hydrogen; acetic acid; In methanol; at 20 ℃; Autoclave; Large scale;

Reference yield: 96.5%

(3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid (486460-00-8,922178-94-7) + 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride (762240-92-6) → sitagliptin (486460-32-6,823817-55-6)

Guidance literature:

(3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid; With triethylamine; In dichloromethane; for 0.166667h;

With benzotriazol-1-ol; dicyclohexyl-carbodiimide; In dichloromethane; at 25 - 30 ℃; for 4h;

3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride; Further stages;

Reference yield: 96.0%

(R,R)-N-benzyl-N-(α-methylbenzyl)-1-(2',4',5'-trifluorophenyl)-4-oxo-4-{3''-(trifluoromethyl)-5'',6''-dihydro-1'',2'',4''-triazolo[4,3-α]pyrazin-7''(8''H)-yl}butan-2-amine (1380521-88-9) → sitagliptin (486460-32-6,823817-55-6)

Guidance literature:

With 30% w/w Pd(OH)2/C; hydrogen; In methanol; for 24h; under 3800.26 Torr;

DOI:10.1016/j.tetlet.2012.04.025

upstream raw materials:

(R)-tert-butyl 4-oxo-4-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-2-ylcarbamate

2,4,5-trifluorobenzyl bromide

3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine

(3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid

Downstream raw materials:

sitagliptin benzoate

Sitagliptin fumarate

sitagliptin oxalate

sitagliptin methanesulfonate

Refernces

• 1、 Clausen, Andrew M.,Dziadul, Brianne,Cappuccio, Kristine L.,Kaba, Mahmoud,Starbuck, Cindy,Hsiao, Yi,Dowling, Thomas M.. "Identification of ammonium chloride as an effective promoter of the asymmetric hydrogenation of a β-enamine amide". . p. 723 - 726. Retrieved 2006.
• 2、 -. "IMPROVED PROCESS FOR PREPARATION OF SITAGLIPTIN". Page/Page column 10-15. . Retrieved 2021/12/31.
• 3、 -. "Preparation method of chiral 4 - aryl - β β-amino acid derivative". . . Retrieved 2021/11/14.