Canagliflozin

Base Information

• Chemical Name: Canagliflozin
• CAS No.: 842133-18-0
• Molecular Formula: C24H25FO5S
• Molecular Weight: 444.524
• Mol file: 842133-18-0.mol

Synonyms:(1S)-1,5-Anhydro-1-(3-{[5-(4-fluorophenyl)-2-thienyl]methyl}-4-methylphenyl)-D-glucitol;

Chemical Property of Canagliflozin

Chemical Property:

• Boiling Point: 642.9±55.0 °C at 760 mmHg
• PKA: 13.34±0.70(Predicted)
• Flash Point: 342.6±31.5 °C
• PSA: 118.39000
• Density: 1.4±0.1 g/cm³
• LogP: 2.96830
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (40 mg/ml)

Purity/Quality:

99% ^*data from raw suppliers

Canagliflozin ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: In March 2013, the US FDA approved canagliflozin (JNJ-28431754; TA-7284) for the treatment of type 2 diabetes in adults. Canagliflozin is the first US-approved sodium-glucose co-transporter (SGLT) inhibitor for the treatment of type 2 diabetes. Inhibition of renal SGLT suppresses glucose reabsorption, which permits glucose excretion into urine and reduction of hyperglycemia. Canagliflozin was discovered through structural modifications of phlorizin, a known inhibitor of renal glucose reabsorption. Early modifications of OH groups on the glucose moiety were insufficient to adequately impair hydrolysis by intestinal β-glucosidase. Introduction of the C-glucoside moiety, as in the clinical candidate dapagliflozin, afforded sufficient resistance to hydrolysis. Finally, incorporation of the thiophene moiety in canagliflozin provided improved potency for hSGLT2 (exclusive to kidney), IC50=2.2 nM, while offering significant selectivity over hSGLT1 (in kidney and heart), IC50=910 nM. Hyperglycemic, high-fat (HF) diet fedmice (KKstrain) that received a single 3 mg/kg oral dose of canagliflozin had a 48% reduction in blood glucose levels after 6 h versus vehicle-treatedmice. Noteworthy in themultistep synthesis of canagliflozin is the stereoselective formation of the β-C-glucoside which is accomplished by coupling of the aryllithiumaglycone with 2,3,4,6-tetra-O-trimethylsilyl-β-Dgluconolactone followed by desilylation and stereoselective reduction with triethylsilane and boron trifluoride etherate.
• Uses: Canagliflozin is a sodium/glucose cotransporter 2 (SGLT2) inhibitor. Canagliflozin has been shown to dose dependently reduce calculated renal threshold for glucose excretion and increase urinary glucose excretion. Canagliflozin is a candidate for the treatment of type 2 diabetes and obesity.
• Clinical Use: Sodium-glucose co-transporter 2 inhibitor: Treatment of type 2 diabetes
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: concentration reduced by rifampicin. Lipid-regulating drugs: avoid canagliflozin for 1 hour before or 4-6 hours after bile acid sequestrants.

Technology Process of Canagliflozin

There total 70 articles about Canagliflozin 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: 99.0%

(2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (866607-35-4) → canagliflozin (842133-18-0,1589590-87-3)

Guidance literature:

With methanol; sodium methylate; at 20 ℃; for 12h; Sealed tube;

DOI:10.1002/adsc.202100343

Reference yield: 96.0%

(2S,3S,4R,5R,6R)-6-(benzoylmethyl)-3,4,5-tribenzoyl-2-{3-[(5-(4-fluorophenyl)-2-thienyl)methyl]-4-methylphenyl}-2H-glucopyranoside → canagliflozin (842133-18-0,1589590-87-3)

Guidance literature:

With sodium methylate; In tetrahydrofuran; methanol; at 40 ℃; for 2h;

Reference yield: 93.3%

C44H45Cl12FO9S → canagliflozin (842133-18-0,1589590-87-3)

Guidance literature:

With water; lithium hydroxide; In methanol; at 0 - 5 ℃; for 16h;

upstream raw materials:

1-[1-hydroxy-2,3,4,6-tetra-O-(trimethylsilyl)-β-D-glucopyranosyl]-4-methyl-3-[[5-(4-fluorophenyl)-2-thienyl]methyl]benzene

(2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

methyl 1-C-(3-{[5-(4-fluorophenyl)-2-thienyl]methyl}-4-methyl-phenyl)-D-glucopyranoside

(2S,3S,4R,5R,6R)-2-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)-6-(pivaloyloxymethyl)tetrahydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate)

Downstream raw materials:

(1S)-1,5-anhydro-1-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D-glucitol hemihydrate

(2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

L-proline-(2S,3R,4R,5S,6R)-2-{3-[5-(4-fluoro-phenyl)-thiophen-2-ylmethyl]-4-methyl-phenyl}-6-hydroxymethyl-tetrahydro-pyran-3,4,5-triol

(2S,3R,4R,5S,6R)-2-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol citric acid co-crystal