960404-48-2 Usage
Uses
Dapagliflozin Propanediol Hydrate is an SGLT2 inhibitor, which can be used for the treatment of diabetes.
Definition
ChEBI: A hydrate that consists of dapagliflozin compounded with (S)-propylene glycol and hydrate in a (1:1:1) ratio. Used to improve glycemic control, along with diet and exercise, in adults with type 2 diabetes.
Clinical Use
The most likely process-scale synthesis has been described in a literature publication and patent, and
this is summarized in the scheme below. The synthesis began with global silylation glucolactone 63
to form tetrasiloxide 64. In parallel, commercial 5-bromo-2-chlorobenzoyl acid (65) was converted to
the corresponding acid chloride with oxalyl chloride. Subsequently, this acid chloride was subjected to
Friedel-Crafts acylation with ethyl phenyl ether (“phenetole”) in the presence of aluminum trichloride at
low temperature to give benzophenone 66 in 91% yield. Next, the carbonyl functionality within 66 was
removed upon treatment with triethylsilane and boron trifluoride-etherate, producing 5-bromo-2-chloro-
4'-ethoxydiphenylmethane 67 in 75% yield as the aglycon partner. Aryl bromide 67 was subjected to lithium halogen exchange conditions and subsequent exposure to lactone 64, which gave a mixture of
lactols which were then immediately subjected to methanesulfonic acid to provide glucol 68 in 85%
yield. The anomeric methoxy group of 68 was reduced with triethylsilane and boron trifluoride-etherate
followed by peracetylation to deliver α-C-glycoside tetra-acetate 69 in 55% (two steps) after
recrystalliaztion in ethanol. Hydrolysis of polyacetate 69 with lithium hydroxide gave dapagliflozin in
quantitative yield, and upon treatment with propanediol in water, dapagliflozin propanediol hydrate (X)
was produced.
Synthesis
Dapagliflozin propanediol hydrate, an orally active sodium glucose cotransporter type 2 (SGLT-2)
inhibitor, was developed by Bristol-Myers Squibb (BMS) and AstraZeneca for the once-daily treatment
of type 2 diabetes. As opposed to competitor SGLT-2 inhibitors, dapagliflozin was not associated with
renal toxicity or long-term deterioration of renal function in phase III clinical trials. The drug exhibits
excellent SGLT2 potency with more than 1200 fold selectivity over the SGLT1 enzyme.
Check Digit Verification of cas no
The CAS Registry Mumber 960404-48-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,6,0,4,0 and 4 respectively; the second part has 2 digits, 4 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 960404-48:
(8*9)+(7*6)+(6*0)+(5*4)+(4*0)+(3*4)+(2*4)+(1*8)=162
162 % 10 = 2
So 960404-48-2 is a valid CAS Registry Number.
960404-48-2Relevant articles and documents
Preparation method of SGLT-2 inhibitor and intermediate
-
Paragraph 0126-0133, (2021/05/19)
The invention discloses a preparation method of an SGLT-2 inhibitor and an intermediate. The method comprises the following steps: (1) reacting a compound A with chlorosilane under the action of an acid-binding agent to generate a compound B; (2) mixing the compound B and a compound C to obtain a compound D; and (3) reacting the compound D with a reducing agent and a catalyst to obtain the SGLT-2 inhibitor compound.
PHARMACEUTICAL FORMULATION CONTAINING AN SGLT2 INHIBITOR
-
Page/Page column 14; 15, (2008/12/07)
Pharmaceutical formulations are provided which are in the form of capsules or tablets for oral use and which include a medicament dapagliflozin or its propylene glycol hydrate and a pharmaceutical acceptable carrier therefor, which formulation is designed for immediate release.
