Canagliflozin

Bezeichnung:Canagliflozin

CAS-Nr842133-18-0

Englisch Name:Canagliflozin

CBNumberCB02510088

SummenformelC24H25FO5S

Molgewicht444.52

MOL-Datei842133-18-0.mol

Canagliflozin physikalisch-chemischer Eigenschaften

Schmelzpunkt	68 - 72°C
Siedepunkt	642.9±55.0 °C(Predicted)
Dichte	1.364
storage temp.	-20°C
Löslichkeit	Soluble in DMSO (40 mg/ml)
Aggregatzustand	solid
pka	13.34±0.70(Predicted)
Farbe	White
Stabilität	Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.
CAS Datenbank	842133-18-0

Sicherheit

Giftige Stoffe Daten

842133-18-0(Hazardous Substances Data)

Gefahreninformationscode (GHS)

Canagliflozin Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
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.
Chemische Eigenschaften
Pale Yellow Solid
Originator
Mitsubishi Tanabe Pharma (Japan)
Verwenden
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.
Definition
ChEBI: A C-glycosyl compound that is used (in its hemihydrate form) for treatment of type II diabetes via inhibition of sodium-glucose transport protein subtype 2.
Trademarks
Invokana
Clinical Use
Sodium-glucose co-transporter 2 inhibitor:

Treatment of type 2 diabetes
target
hSGLT2
Arzneimittelwechselwirkung
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.
Stoffwechsel
O-glucuronidation is the major metabolic elimination pathway mainly by UGT1A9 and UGT2B4 to two inactive metabolites. CYP3A4-mediated (oxidative) metabolism of canagliflozin is minimal (approximately 7%) in humans.
Einzelnachweise
Nomura et al. (2010), Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus; J. Med. Chem., 53 6355 Shaw et al. (2011), Canagliflozin, a novel inhibitor of sodium glucose co-transporter 2, dose dependently reduces calculated renal threshold for glucose excretion and increases urinary glucose excretion in healthy subjects; Diabetes Obes. Metab., 13 669 Mantovani et al. (2020), Sodium-Glucose Cotransporter-2 Inhibitors for Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials; Metabolites, 11 22 Miller et al. (2020), Canagliflozin extends life span in genetically heterogeneous male but not female mice; JCI Insight, 5 e140019 Vilani et al. (2016), The diabetes medication Canagliflozin reduces cancer cell proliferation by inhibiting mitochondrial complex-I supported respiration; Mol. Metab., 5 1048 Xu et al. (2020), Inhibitory effects of canagliflozin on pancreatic cancer are mediated via the downregulation of glucose transporter-1 and lactate dehydrogenase A; Int. J. Oncol. 57 1223

Canagliflozin Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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