Saxagliptin

Base Information

• Chemical Name: Saxagliptin
• CAS No.: 945667-22-1
• Molecular Formula: C18H25N3O2.H2O
• Molecular Weight: 333.431
• NSC Number: 760407
• UNII: 8I7IO46IVQ
• DSSTox Substance ID: DTXSID7048580
• Wikipedia: Saxagliptin
• Wikidata: Q3121121
• NCI Thesaurus Code: C75984
• RXCUI: 1546030
• Pharos Ligand ID: FUTJN139DA3R
• Metabolomics Workbench ID: 43670
• ChEMBL ID: CHEMBL385517
• Mol file: 945667-22-1.mol

Synonyms:3-hydroxyadamantylglycine-4,5-methanoprolinenitrile hydrate;BMS 477118;BMS-477118;BMS477118;Onglyza;saxagliptin

Chemical Property of Saxagliptin

Chemical Property:

• Appearance/Colour: White solid
• PSA: 99.58000
• LogP: 1.73188
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO (Slightly), Methanol (Sparingly)
• XLogP3: 0.7
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 2
• Exact Mass: 315.19467705
• Heavy Atom Count: 23
• Complexity: 609

Purity/Quality:

99.9% ^*data from raw suppliers

SaxagliptinHydrate ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antidiabetic Agents
• Canonical SMILES: C1C2CC2N(C1C#N)C(=O)C(C34CC5CC(C3)CC(C5)(C4)O)N
• Isomeric SMILES: C1[C@@H]2C[C@@H]2N([C@@H]1C#N)C(=O)[C@H](C34CC5CC(C3)CC(C5)(C4)O)N
• Recent ClinicalTrials: Study to Evaluate Safety and Efficacy of Dapagliflozin and Saxagliptin in Patients With Type 2 Diabetes Mellitus Aged 10 to Below 18 Years Old
• Recent EU Clinical Trials: Effectiveness of Dapagliflozin + Saxagliptin to revert from a standard basalbolus
• Recent NIPH Clinical Trials: Effect of omarigliptin on glucose variability and oxidative stress in type 2 diabetes patients
• Description: While liraglutide targets the incretin system as a GLP-1 analog for therapeutic intervention in T2DM, saxagliptin enhances GLP-1 plasma concentrations by inhibiting the DPP-4 enzyme responsible for degradation of GLP-1 by cleavage of the two N-terminal amino acids adjacent to alanine (or proline), thereby rendering the hormone inactive. Similarto vildagliptin, saxagliptin is a cyanopyrrolidine substrate-based inhibitor. The proline mimetic occupies the small S1-pocket while the nitrile’s trajectory aligns with the scissile bond of the substrate. The slow dissociation kinetics of saxagliptin is attributed to a reversible, covalent reaction between the nitrile and the catalytically active serine hydroxyl (Ser630). The steric bulk provided by the adamantyl moiety and the constrained cyclopropyl ring stabilizes the trans-rotamer of the amide, thereby preventing the problematic intramolecular cyclization, via the amino group attacking the nitrile, which is favored in the cis-conformation. Since metabolism of saxagliptin is primarily mediated by CYP3A4/5, there is a potential for drug interactions with concomitant administration of strong inducers or inhibitors of these cytochrome P450 enzymes. The most common adverse events (>5% of patients) included upper respiratory tract infection, urinary tract infection, and headache.
• Uses: Saxagliptin Hydrate is a selective and reversible dipeptidyl peptidase-4 (DPP4) inhibitor that may be used to develop treatment for type 2 diabetes.

Technology Process of Saxagliptin

There total 2 articles about Saxagliptin 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: 81.0%

3-cyano-(αS)-α-(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)-β-oxo-(1S,3S,5S)-2-azabicyclo[3.1.0]hexane-2-ethanecarbamic acid 1,1-dimethylethyl ester (709031-43-6) → saxagliptin monohydrate (945667-22-1)

Guidance literature:

3-cyano-(αS)-α-(3-hydroxytricyclo[3.3.1.1^3,7]dec-1-yl)-β-oxo-(1S,3S,5S)-2-azabicyclo[3.1.0]hexane-2-ethanecarbamic acid 1,1-dimethylethyl ester; With hydrogenchloride; In methanol; dichloromethane; water; for 18h;

With sodium hydroxide; water; In methanol; dichloromethane; for 0.333333h; pH=9.0 - 10.5; Product distribution / selectivity;

Reference yield:

saxagliptin (1564265-93-5) → saxagliptin monohydrate (945667-22-1)

Guidance literature:

With water; In ethyl acetate; isopropyl alcohol; at 65 ℃;

Reference yield:

saxagliptin monohydrate (945667-22-1) → saxagliptin dihydrochloride dihydrate (1370409-28-1,1073057-20-1)

Guidance literature:

With hydrogenchloride; In 1,4-dioxane; ethanol; at 20 ℃;

upstream raw materials:

3-cyano-(αS)-α-(3-hydroxytricyclo[3.3.1.1^3,7]dec-1-yl)-β-oxo-(1S,3S,5S)-2-azabicyclo[3.1.0]hexane-2-ethanecarbamic acid 1,1-dimethylethyl ester

saxagliptin

Downstream raw materials:

saxagliptin dihydrochloride dihydrate

saxagliptin

Refernces

• 1、 -. "CRYSTAL FORMS OF SAXAGLIPTIN AND PROCESSES FOR PREPARING SAME". Page/Page column 27-28. . Retrieved 2008/12/08.