Canagliflozin heMihydrate CAS 928672-86-0

Introduction：Basic information about Canagliflozin heMihydrate CAS 928672-86-0, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Canagliflozin heMihydrate Basic information

• Product Name: Canagliflozin heMihydrate
• Synonyms: Cagliflozin heMihydrate;Canagliflozin hydrate (2:1);Canagliflozin heMihydrate;D-Glucitol, 1,5-anhydro-1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]Methyl]-4-Methylphenyl]-, hydrate (2:1);Canagliflozin heMihydrates;(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 Hemihydrate;(1S)-1,5-Anhydro-1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D-glucitol hydrate (2:1);Cageline
• CAS: 928672-86-0
• MF: 2(C24H25FO5S).H2O
• MW: 462.53
• EINECS: 202-303-5
• Product Categories: Canagliflozin;API;928672-86-0
• Mol File: 928672-86-0.mol

Canagliflozin heMihydrate Chemical Properties

• Melting point: 94-96°C
• storage temp.: Hygroscopic, Refrigerator, under inert atmosphere
• solubility: DMSO (Slightly), Methanol (Slightly)
• form: Solid
• color: White to Off-White
• Optical Rotation: 19.1°(C=0.01g/mL, MEOH, 20°C, 589nm)
• Stability: Hygroscopic
• InChIKey: RCCZPUWDQVUJAB-HNJBBDRUNA-N
• SMILES: O[C@@H]1[C@H]([C@H](O)[C@@H](CO)O[C@H]1C1C=CC(C)=C(CC2=CC=C(C3C=CC(F)=CC=3)S2)C=1)O.O |&1:1,2,3,5,9,r|

Canagliflozin heMihydrate Usage And Synthesis

Description

Canagliflozin, an orally active and selective sodium–glucosecotransporter 2 (SGLT2) inhibitor, was co-developed byMitsubishi Tanabe Pharma and Johnson & Johnson (J&J) for thetreatment of type 2 diabetes mellitus (T2DM) and obesity. Thedrug was approved in March by the U.S. FDA and launched inApril 2013 in the U.S. SGLT2 is involved in the glucose re-absorptionpathway in the kidney, and its inhibition increases urinaryglucose excretion, and reduces plasma glucose and HbA1c levels.In addition, canagliflozin is safe in combination with other commonlyused antidiabetic agents and has a significant effect on bodyweight reduction. A recently published process patent fromScinoPharm Taiwan describes the synthesis of canagliflozin.

Uses

Canagliflozin Hemihydrate is a derivative of Canagliflozin (C175190), which 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: Canagliflozin hydrate is a hydrate that is the hemihydrate form of canagliflozin. Used for treatment of type II diabetes via inhibition of sodium-glucose transport protein subtype 2. It has a role as a hypoglycemic agent and a sodium-glucose transport protein subtype 2 inhibitor. It contains a canagliflozin.

Synthesis

Synthesis of the aglycone region of canagliflozin was describedin a separate patent by first condensing commercially available 5-bromo-2-methylbenzoyl chloride (14) and 2-(4-fluorophenyl)-thiophene (15) under Friedel¨CCrafts acylation conditions to giveketone 16 in 69% yield as a crystalline solid. Ketone 16 was thenreduced with triethylsilyl hydride in the presence of BF3Et2O atlow temperature to give aglycone bromide 17 in 70% yield. Theprecursor for the glycoside moiety, commercially available glycosidetriol 18, was selectively treated with t-butyldiphenylsilylchloride (TBDPSCl) in THF in the presence of imidazole to givethe bis-silyl ether 19 in 81% yield. Next, a unique, stereospecificb-C-arylglucosidation was developed to secure the union of theaglyone- and glycoside-containing portions of canagliflozin.Bromide 17 was subjected to magnesium powder under standardGrignard conditions prior to treatment with AlCl3 in THF in situ.This resulting mixture was then exposed to a solution of compound19 in PhOMe which had been pre-treated with n-BuLi, and the entire mixture was then warmed to 150 ?? for 5 h to ultimatelygive the b-anomer 20 in 56% yield. Finally, removal of the silylgroups within 20 with tetrabutyl ammonium fluoride (TBAF) inTHF delivered canagliflozin hydrate (III) in 73% yield.

in vivo

Canagliflozin (30 mg/kg treatment for 4 weeks) reduces blood glucose (BG) levels, respiratory exchange ratio, and body weight gain in DIO mice^[1].
Canagliflozin (3 mg/kg for 3 weeks) increases urinary glucose excretion (UGE) with no significant change in total food intake compared with that in vehicle-treated rats, leading to a decrease in body weight In ZF rats^[1].

• Animal Model: Diet-induced obese, insulin resistantmice (DIO) Mice^[1]
• Dosage: 30 mg/kg
• Administration: Oral gavage; daily; 4 weeks
• Result: Reduced BG levels, respiratory exchange ratio, and body weight gain.

• Animal Model: Male Zucker fatty (ZF) obese, insulin resistant rats^[1]
• Dosage: 3 mg/kg
• Administration: Oral gavage; daily; 3 weeks
• Result: UGE was increased with no significant change in total food intake compared with that in vehicle-treated rats, leading to a decrease in body weight.

IC 50

SGLT2