Empagliflozin

Bezeichnung:Empagliflozin

CAS-Nr864070-44-0

Englisch Name:Empagliflozin

CBNumberCB52627802

SummenformelC23H27ClO7

Molgewicht450.91

MOL-Datei864070-44-0.mol

Empagliflozin physikalisch-chemischer Eigenschaften

Siedepunkt	665℃
Dichte	1.398
Flammpunkt	356℃
storage temp.	2-8°C
Löslichkeit	insoluble in H2O; ≥20.75 mg/mL in DMSO; ≥7.06 mg/mL in EtOH with ultrasonic
Aggregatzustand	solid
pka	13.23±0.70(Predicted)
Farbe	White
Stabilität	Hygroscopic
InChIKey	OBWASQILIWPZMG-QZMOQZSNSA-N
SMILES	C1=C(CC2=CC([C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)=CC=C2Cl)C=CC(O[C@H]2CCOC2)=C1

Gefahreninformationscode (GHS)

Empagliflozin Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, was originally discovered by Boehringer Ingelheim and codeveloped and co-marketed through research collaboration with Eli Lilly and Co. It was first approved by European Medicine Agency (EMA) in May 2014, followed by the approval of the US FDA in August 2014. SGLT2 inhibitors are anewclass of glucose-lowering agents developed for the treatment of type 2 diabetes mellitus, which have a mechanism of action that is independent of pancreatic b-cell function or the degree of insulin resistance. Consequently, SGLT2 inhibitors have the potential to be of use not only as standalone therapy but also in combination with any of the existing classes of glucose-lowering agents, including insulin. Empagliflozin selectively inhibits SGLT2, which in turn prevents glucose reabsorption by excreting excess glucose in the urine.
Verwenden
Empagliflozin is a novel, potent and selective SGLT-2 inhibitor, improves glycaemic control and features of metabolic syndrome in diabetic rats.
Definition
ChEBI: Empagliflozin is a C-glycosyl compound consisting of a beta-glucosyl residue having a (4-chloro-3-{4-[(3S)-tetrahydrofuran-3-yloxy]benzyl}phenyl group at the anomeric centre. A sodium-glucose co-transporter 2 inhibitor used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It has a role as a sodium-glucose transport protein subtype 2 inhibitor and a hypoglycemic agent. It is a C-glycosyl compound, an aromatic ether, a tetrahydrofuryl ether and a member of monochlorobenzenes.
Clinical Use
Selective and reversible inhibitor of sodium-glucose co-transporter 2:
Treatment of type 2 diabetes
Nebenwirkungen
Empagliflozin had a low incidence of adverse reactions. Compared with the placebo group, the incidence of common adverse reactions was 2%, including urinary tract infection, female reproductive system fungal infection, upper respiratory tract infection, polyuria, dyslipidemia (dose-related low-density lipoprotein increased), arthralgia, fungal infection of male reproductive system, hypoglycemia (the incidence of hypoglycemia increased when empagliflozin was combined with insulin or sulfonylurea hypoglycemic drugs), nausea. Other adverse reactions less than 2% were common in thirst (polydipsia, polydipsia), hypovolemia, and renal dysfunction.
Synthese
Commercial 5-iodo-2-chlorobenzoic acid (97) was first converted to the corresponding acid chloride, prior to subjection to commercially available fluorobenzene (98) under Friedel¨CCrafts conditions to generate the desired fluorobenzophenone 99 in 94% yield after isolation by recrystallization from aqueous isopropanol. The fluorobenzophenone (99) was then reacted with commercially available (S)-3-hydroxytetrahydrofuran (100) and potassium tertbutoxide in THF to afford ethereal benzophenone 101. Next, removal of the ketone functionality within 101 was achieved through the use of 1,1,3,3-tetramethyldisiloxane (TMDS) in the presence of aluminum chloride in toluene to deliver diaryl iodide 102. This iodide was subsequently converted to the corresponding Grignard reagent and subjected to gluconolactone 103, giving rise to an intermediate lactol which was then sequentially treated with aqueous citric acid, methanolic HCl, and triethylsilyl hydride and aluminum trichloride to ultimately furnish empagliflozin (XIII) in 73% yield across the four-step protocol.
target
SGLT-2
Stoffwechsel
In vitro studies suggested that the main route of metabolism is glucuronidation by the uridine 5'-diphospho-glucuronosyltransferases UGT2B7, UGT1A3, UGT1A8, and UGT1A9
Following administration of oral [14C]-empagliflozin solution to healthy volunteers, approximately 96% of the drug-related radioactivity was eliminated in faeces (41%) or urine (54%). The majority of drug-related radioactivity recovered in faeces was unchanged parent drug and approximately half of drug-related radioactivity excreted in urine was unchanged parent drug
Lager
-20°C
Mode of action
Empagliflozin is an orally available competitive inhibitor of sodium-glucose co-transporter 2 (SGLT2; SLC5A2) with antihyperglycemic activity. Upon oral administration, empagliflozin selectively and potently inhibits SGLT2 in the kidneys, thereby suppressing the reabsorption of glucose in the proximal tubule. Inhibition of SGLT2 increases urinary glucose excretion by the kidneys, resulting in a reduction of plasma glucose levels in an insulin-independent manner. Inhibition of SGLT2 in the kidneys also suppresses the renal reabsorption of 1,5-anhydroglucitol (1,5AG). This lowers serum 1,5AG and neutrophil 1,5-anhydroglucitol-6-phosphate (1,5AG6P) levels, which may improve neutropenia and neutrophil dysfunction in patients with glycogen storage disease type Ib (GSD Ib). SGLT2, a transport protein exclusively expressed in the proximal renal tubules, mediates approximately 90% of renal glucose reabsorption from tubular fluid.
pubchem.ncbi.nlm.nih.gov/compound/Empagliflozin

Empagliflozin Upstream-Materialien And Downstream Produkte

Empagliflozin Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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