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Dapagliflozin

Diabetes drugs Pharmacological effects Pharmacokinetics Synthesis method Safety Drug interactions
Dapagliflozin
Dapagliflozin structure
CAS No.
461432-26-8
Chemical Name:
Dapagliflozin
Synonyms
CS-179;Dagliel;Farxiga;Daglican;Bms 512148;BMS5121458;Dagliejing;Dagagflozin;Dapagliflozi;apagliflozin
CBNumber:
CB91011730
Molecular Formula:
C21H25ClO6
Formula Weight:
408.88
MOL File:
461432-26-8.mol

Dapagliflozin Properties

Boiling point:
609.0±55.0 °C(Predicted)
Density 
1.349
storage temp. 
Sealed in dry,2-8°C
pka
13.23±0.70(Predicted)
FDA UNII
1ULL0QJ8UC
NCI Drug Dictionary
dapagliflozin

Dapagliflozin price More Price(4)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Cayman Chemical 11574 Dapagliflozin ≥98% 461432-26-8 1mg $25 2021-03-22 Buy
Cayman Chemical 11574 Dapagliflozin ≥98% 461432-26-8 5mg $94 2021-03-22 Buy
Cayman Chemical 11574 Dapagliflozin ≥98% 461432-26-8 10mg $150 2021-03-22 Buy
Cayman Chemical 11574 Dapagliflozin ≥98% 461432-26-8 50mg $375 2021-03-22 Buy

Dapagliflozin Chemical Properties,Uses,Production

Diabetes drugs

Dapagliflozin (ForxigaTM) is a new antidiabetic drug jointly developed by Bristol-Myers Squibb and AstraZeneca, being approved by the European Medicines Agency (EMA) on November 12, 2012. It is also the first approved SGLT2 inhibitor for the treatment of type II diabetes, being an important option in the treatment of diabetes, and is used to improve glycemic control as an adjunct to dietary and exercise for adults with type II diabetes.
Dapagliflozin is a sodium-glucose co-transporter 2 inhibitor. On January 8, 2014, the US Food and Drug Administration (FDA) have approved it for being used in the treatment of type II diabetes. Meanwhile, FDA requires the producers to conduct post-marketing research on drug-related risks.
The post-marketing trial requested by the FDA includes a cardiovascular outcome trial for assessing the cardiovascular risk for high-risk patients after treatment with dapagliflozin at baseline and a study to assess the risk of bladder cancer in recruited patients. Another study will assess the bladder tumor-promoting effect of this drug on rodent animals. Two studies will assess the pharmacokinetics, efficacy and safety of dapagliflozin in pediatric patients; a set of strengthened pharmacovigilance program will monitor liver abnormalities and pregnancy outcome reports in patients receiving daglitazone. Dapagliflozin will be marketed under the tradename Farxiga by Haoeyou Pharmacy.
The above information is edited by Andy of chemicalbook.

Pharmacological effects

Dapagliflozin works through inhibiting sodium-glucose transporter 2 (SGLT2), a protein in the kidney that reabsorbs glucose into the bloodstream. This allows extra glucose to be excreted through the urine, improving glycemic control without increasing insulin secretion. The use of this drug requires patients with normal renal function while patients of moderate to severe renal insufficiency should be disabled to use this drug. Single application of this product or combination with metformin, pioglitazone, glimepiride, insulin and other drugs can significantly reduce the HbA1c and fasting blood glucose of patients suffering type II diabetes. The frequency of the adverse reaction was similar to placebo with low risk of hypoglycemia, being able to reduce body weight.
The efficacy of dapagliflozin is comparable with the dipeptidyl peptidase inhibitors, and several new hypoglycemic drugs, and can also mildly lower the blood pressure and body weight. The drug has 5mg and 10mg two tablets to choose from, can be either used alone or together with insulin, including other diabetes drugs.

Pharmacokinetics

In healthy subjects, dapagliflozin was rapidly absorbed after oral administration with a peak time Tmax being 1 to 2 hours, a protein binding rate of 91%, an oral bioavailability of about 78% and a plasma terminal half-life of 12.9 hours. After oral administration, the drug is mainly metabolized by the uridine diphosphate glucuronosyltransferase 1A9 (UGT1A9) into the inactive metabolite in the liver with the smaller part being metabolized by the P450 enzyme and of no inhibitory or inducing effect on the P450 enzyme. Drug prototypes and related metabolites were excreted through urine (75%) and faeces (21%). Compare simultaneous administration of this product with high-fat food and with the fasting administration, Tmax can be extended by 1-fold, but the absorption did not affect the degree, so can be administrated together with the food.
The pharmacokinetics of daglitazone was significantly affected by renal function. Diabetic patients with mild, moderate or severe renal insufficiency are merged to be subject to oral administration of 20 mg • d-1 daglitazone for 7 days. The mean systemic exposure amount, compared with patients with normal renal function, is respectively 32%, 60% and 87% higher. For patients with normal renal function, mild insufficiency, moderate insufficiency and severe insufficiency, the urinary glucose excretion amount in 24 hours of steady state was 85, 52, 18 and 11g, successively.
Kasichayanula et al have studied the pharmacokinetic effects of liver dysfunction on daglitazone. The patients with mild, moderate and severe hepatic insufficiency having a single oral dose of 10 mg of daglitazone, the Cmax of each group was 12% lower, 12% higher and 40% higher than that with normal liver function, respectively. The AUC of each group was significantly higher than that of normal liver function by 3%, 36% and 67%.
Therefore, it is not recommended to apply daglitazone to patients of moderate and severe renal dysfunction. Severe liver dysfunction patients need to reduce the use of dose.

Synthesis method

5-bromo-2-chlorobenzoic acid is subject to acylating chlorination, and has Friedel-Crafts reaction with phenylethyl ether for reduction of its carbonyl group, generating 5-bromo-2-chloro-4'-ethoxydiphenyl methane, further subjecting to condensation with 2, 3, 4, 6-tetra-O-trimethylsilyl-D-glucopyranosanoic acid-1,5-lactone. The anomeric carbon hydroxyl group is subject to etherification and deprotection to give 2-chloro-5-(1-methoxy-D-glucopyranose-I-yl)-4'-ethoxydiphenylmethane, and then use Et3SiH/BF3 • OEt2 for reduction to remove methoxy, followed by acetic anhydride esterification and hydrolysis to give hypoglycemic agents daglitazone with the overall yield of about 40%.
the chemical reaction route of synthesizing dapagliflozin
Fig.1 shows the chemical reaction route of synthesizing dapagliflozin.

Safety

Daglitazone has excellent tolerance and safety with the incidence of adverse events associated with 10 mg • d-1 daglitazone being similar to that of placebo. Common adverse events included hypoglycemia, polyuria, back pain, genital infections, urinary tract infections, dyslipidemia and hematocrit (HCT) increase. The overall risk of hypoglycemia is low, and the incidence of hypoglycemia is associated with other basic hypoglycemic agents. The incidence of hypoglycemia was higher in patients subjecting to joint treatment between daglitazone and sulfonylureas or insulin compared with placebo. Therefore, when this product is used in combination with insulin or insulin secretagogue, you may need to adjust the dose of the latter one.

Drug interactions

This product is mainly metabolized in the liver by UGT1A9 metabolism, being the P-glycoprotein substrate. Study confirmed that the pharmacokinetics of daglitazone was not affected by metformin, pioglitazone, sitagliptin, glimepiride, voglibose, and simvastatin, valsartan, warfarin, and digoxin. The serum concentrations of the above-mentioned drugs are also not clinically significantly affected by daglitazone. Rifampicin can reduce the exposure amount of daglitazone by 22% while mefenamic acid can increase the body exposure amount by 51%, but have no clinically significant effect on 24 h urine glucose excretion.

Description

The Australian Therapeutic Goods Administration (TGA) and the European Commission approved dapagliflozin in October and November 2012, respectively, as an adjunct to diet and exercise for the treatment of type 2 diabetes. Dapagliflozin is a potentially attractive therapy due to its glucosesensitive and insulin-independent mechanism of action. It is a first-in-class selective SGLT2 inhibitor (IC50=1.1 nM; selectivity vs. SGLT1 >1000) that lowers the renal threshold for reabsorption of glucose, allowing excess glucose to be eliminated via the kidneys. In normal rats, administration of dapagliflozin promotes dose-dependent excretion of up to 1900 mg of glucose over a 24 h period, with amaximal effect at 3 mg/kg. In a ratmodel of diabetes, pretreatment with the pancreatic toxin streptozotocin results in hyperglycemia that is reduced 55% by administration of a single 0.1 mg/kg dose of dapagliflozin compared with vehicle. Aryl O-glucoside SGLT2 inhibitors were early entrants into the clinic, but the aryl C-glucoside linkage found in dapagliflozin confers resistance to glucosidase-mediated metabolism leading to improved clinical utility relative to aryl O-glucosides. The modified carbohydrate–aglycone linkage required concomitant adjustment from an ortho- to a meta-substituted arylglucoside to achieve potent SGLT2 inhibition. Dapagliflozin was synthesized in several steps via reaction of an aryllithium with per-silylated gluconolactone to form the key C-glucoside linkage. An alpha-selective reduction of the resultant anomeric glycoside gave the desired beta-Carylglucoside. The main circulating (inactive) metabolite is the result of 3-O-glucuronidation of the glucosylmoiety. Of the minority metabolites, the main oxidative species result from O-dealkylation of the ethoxy-group and hydroxylation of the biarylmethane moiety.

Chemical Properties

White Solid

Originator

Bristol-Myers Squibb (United States)

Uses

A sodium-glucose transporter 2 inhibitor.

Uses

therapeutic for diabetes I or II, and hyperglycemia

Definition

ChEBI: A C-glycosyl comprising beta-D-glucose in which the anomeric hydroxy group is replaced by a 4-chloro-3-(4-ethoxybenzyl)phenyl group. Used (in the formo f its propanediol monohydrate) to improve glycemic ontrol, along with diet and exercise, in adults with type 2 diabetes.

brand name

Forxiga

Dapagliflozin Preparation Products And Raw materials

Raw materials

Preparation Products


Dapagliflozin Suppliers

Global( 412)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Anqing Chico Pharmaceutical Co., Ltd.
15380796838
chloewu@chicopharm.cn CHINA 341 58
Echemi Group
18905328650 86-18905328650
pharma@echemi.com CHINA 215 58
Shenzhen Shengda Pharma Limited
+86-755-85269922
WeChat:shengdapharm sales@shengdapharm.com CHINA 230 58
Henan DaKen Chemical CO.,LTD.
+86-371-66670886
info@dakenchem.com China 21031 58
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com CHINA 22607 55
Hangzhou FandaChem Co.,Ltd.
008615858145714
+86-571-56059825 fandachem@gmail.com CHINA 8882 55
Nanjing ChemLin Chemical Industry Co., Ltd.
025-83697070
product@chemlin.com.cn CHINA 3013 60
Shanghai Yingrui Biopharma Co., Ltd.
+86-21-33585366 E-mail:sales03@shyrchem.com
+86-21-34979012 sales03@shyrchem.com CHINA 739 60
ATK CHEMICAL COMPANY LIMITED
+86 21 5161 9050/ 5187 7795
+86 21 5161 9052/ 5187 7796 ivan@atkchemical.com CHINA 26734 60
Lianyungang happen teng technology co., LTD
15950718863
wang666xt@163.com CHINA 296 58

View Lastest Price from Dapagliflozin manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2021-09-29 Dapagliflozin
461432-26-8
US $0.00 / Kg/Bag 100g 99%min 20kg WUHAN FORTUNA CHEMICAL CO., LTD
2021-08-19 Dapagliflozin USP/EP/BP
461432-26-8
US $1.10 / g 1g 99.9% 100 Tons min Dideu Industries Group Limited
2021-08-12 Dapagliflozin
461432-26-8
US $0.00 / Kg/Bag 2Kg/Bag 99% min / GMP application / PMDA / DMF 20 tons Sinoway Industrial co., ltd.

461432-26-8(Dapagliflozin)Related Search:


  • DAPAGLIFLOZIN
  • (1S)-1,5-Anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-D-glucitol
  • Dapagliflozin propanediol
  • BMS-512148-05
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  • D-Glucitol, 1,5-anhydro-1-C-(4-chloro-3-((4-ethoxyphenyl)methyl)phenyl)-, (1S)-
  • Dapagliflozin(BMS-512148)
  • (2S,4R,5R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxyMethyl)tetrahydro-2H-pyran-3,4,5-triol
  • 1-[4-Chloro-3-(4-ethoxybenzyl)phenyl]-1-deoxy-beta-D-glucopyranose (1S)-1,5-Anhydro-1-C-[4-chloro-3-(4-ethoxybenzyl)phenyl]-D-glucitol (2S,3R,4R,5S,6R)-2-[4-Chloro-3-(4-ethoxybenzyl)phenyl]-6-(hydroxyMethyl)tetrahydro-2H-pyran-3,4,5-triol
  • (2S,3R,4R,5S,6R)-2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxyMethyltetrahydro-2H-pyran-3,4,5-triol
  • 1-[4-Chloro-3-(4-ethoxybenzyl)phenyl]-1-deoxy-beta-D-glucopyranose
  • BMS5121458
  • Dag coluMn net
  • Dapagliflozin Propanediol Monohydrate
  • Dapagliflozin Isomer Impurity
  • Dapagliflozin, >=98%
  • Dapagliflozin fandachem
  • apagliflozin
  • Farxiga
  • Dapagliflozin USP/EP/BP
  • Dagagflozin
  • Dagliejing
  • 461432-26-8
  • 61432-26-8
  • 46132-26-8
  • 461432-26-8;960404-48-2
  • C21H25ClO6
  • Inhibitors
  • Other APIs
  • APIs
  • Aromatics
  • Heterocycles
  • Intermediates & Fine Chemicals
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