Canagliflozin , ≥98% , 842133-18-0

CAS NO.：842133-18-0

Empirical Formula: C24H25FO5S

Molecular Weight: 444.52

MDL number: MFCD18251436

EINECS: 695-192-1

PRODUCT Properties

• Melting point: 68 - 72°C
• Boiling point: 642.9±55.0 °C(Predicted)
• Density: 1.364
• storage temp.: -20°C
• solubility: Soluble in DMSO (40 mg/ml)
• pka: 13.34±0.70(Predicted)
• form: solid
• color: White
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.

Description and Uses

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.

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.

Safety

• Symbol(GHS): GHS08,GHS05
• Signal word: Danger
• Hazard statements: H361-H318
• Precautionary statements: P280-P305+P351+P338-P310-P201-P202-P281-P308+P313-P405-P501