945667-22-1

Basic information

• Product Name: Saxagliptin hydrate
• Synonyms: Saxagliptin hydrate;Saxagliptin hydrate Unii-9gb927lajw;(1S,3S,5S)-2-[(2S)-2-Amino-2-(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile hydrate;Saxagliptin Monohydrate;Saxagliptin hydrate (1S,3S,5S)-2-[(2S)-2-Amino-2-(3-hydroxytricyclo[3.3.1.1(3,7)]dec-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile hydrate;2-Azabicyclo[3.1.0]hexane-3-carbonitrile, 2-[(2S)-2-amino-2-(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)acetyl]-, hydrate (1:1), (1S,3S,5S)-
• CAS NO: 945667-22-1
• Molecular Formula: C₁₈H₂₅N₃O₂*H₂O
• Molecular Weight: 333.43
• EINECS: 1308068-626-2
• Product Categories: Saxagliptin hydrate
• Mol File: 945667-22-1.mol
• Article Data: 2

Chemical Properties

• Appearance: White solid
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Sparingly)
• CAS DataBase Reference: Saxagliptin hydrate(CAS DataBase Reference)
• NIST Chemistry Reference: Saxagliptin hydrate(945667-22-1)
• EPA Substance Registry System: Saxagliptin hydrate(945667-22-1)

Safety Data

• Hazardous Substances Data: 945667-22-1(Hazardous Substances Data)

Usage

Description

Saxagliptin hydrate, also known as Onglyza, is a selective and reversible dipeptidyl peptidase-4 (DPP4) inhibitor used for the treatment of type 2 diabetes. It enhances GLP-1 plasma concentrations by inhibiting the DPP-4 enzyme responsible for the degradation of GLP-1, a hormone that plays a crucial role in glucose homeostasis. Saxagliptin is a cyanopyrrolidine substrate-based inhibitor with a unique structure that provides slow dissociation kinetics and stability.

Uses

Used in Pharmaceutical Industry:
Saxagliptin hydrate is used as an antidiabetic drug for the treatment of type 2 diabetes. It works by inhibiting the DPP-4 enzyme, which is responsible for the degradation of GLP-1, a hormone that helps regulate blood glucose levels. By increasing the levels of active GLP-1, saxagliptin hydrate helps improve glycemic control and reduce blood sugar levels in patients with type 2 diabetes.
Used in Drug Metabolism Studies:
Saxagliptin hydrate is used in research to study the role of cytochrome P450 enzymes, specifically CYP3A4/5, in drug metabolism. Since metabolism of saxagliptin is primarily mediated by these enzymes, it serves as a useful model for understanding drug interactions and potential side effects when other medications are administered concurrently.
Used in Clinical Trials and Research:
Saxagliptin hydrate is used in clinical trials and research studies to evaluate its efficacy and safety in the treatment of type 2 diabetes. These studies help to determine the optimal dosage, potential side effects, and long-term benefits of using saxagliptin hydrate as a therapeutic intervention for diabetes management.
Used in Drug Interaction Studies:
Saxagliptin hydrate is used in studies to investigate potential drug interactions with other medications, particularly those that are strong inducers or inhibitors of cytochrome P450 enzymes. Understanding these interactions is crucial for ensuring patient safety and effective diabetes management.

Originator

Bristol-Myers-Squibb (US)

InChI:InChI:1S/C18H25N3O2.H2O/c19-8-13-2-12-3-14(12)21(13)16(22)15(20)17-4-10-1-11(5-17)7-18(23,6-10)9-17;/h10-15,23H,1-7,9,20H2;1H2

Synthetic route

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)

Conditions	Yield
Stage #1: 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 With hydrogenchloride In methanol; dichloromethane; water for 18h; Stage #2: With sodium hydroxide; water In methanol; dichloromethane for 0.333333h; pH=9.0 - 10.5; Product distribution / selectivity;	81%
Stage #1: 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 With hydrogenchloride In water; ethyl acetate at 23℃; for 4h; Stage #2: With water; potassium carbonate In ethyl acetate at 16 - 20℃; for 2h; Product distribution / selectivity;	77%
Stage #1: 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 With hydrogenchloride In water; isopropyl alcohol at 65℃; for 1.5h; Stage #2: With sodium hydroxide; water; potassium carbonate In dichloromethane; isopropyl alcohol pH=~ 9; Product distribution / selectivity;

saxagliptin → saxagliptin monohydrate (945667-22-1)

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

saxagliptin monohydrate (945667-22-1) → saxagliptin dihydrochloride dihydrate

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

saxagliptin monohydrate (945667-22-1) → saxagliptin

Conditions	Yield
Stage #1: saxagliptin monohydrate In dichloromethane; isopropyl alcohol Stage #2: In ethyl acetate

Upstream product

• 709031-43-6 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 
• 1564265-93-5 saxagliptin 

Downstream Products

• 1370409-28-1 saxagliptin dihydrochloride dihydrate 
• 1564265-93-5 saxagliptin 

Relevant articles and documents

A sand geleg sandbank salt and its preparation method

The invention relates to a saxagliptin salt and a preparation method thereof. The saxagliptin salt has a structure represented by the formula II. Saxagliptin p-toluene sulfonate with a stable crystal form can be obtained through the salt-forming reactions between saxagliptin free alkali and p-toluene sulfonic acid under different solution systems. Stability researches show that saxagliptin p-toluene sulfonate has a better thermal stability than that of saxagliptin monohydrate and saxagliptin hydrochloride. Moreover, the preparation method of the saxagliptin salt is simple and is suitable for industrial production.