761423-87-4 Usage
Description
Ipragliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor (IC50 = 7.4 nM in CHO cells expressing the human cotransporter). It is selective for SGLT2 over SGLT1, SGLT3, SGLT4, SGLT5, and SGLT6 (IC50s = 1.9, 30.4, 15.9, 0.46, and 10.4 μM, respectively). Ipragliflozin (0.1-3 mg/kg) decreases plasma levels of insulin and glucose in an oral glucose tolerance test in a mouse model of diabetes induced by high-fat diet, streptozotocin (STZ; ), and nicotinamide . It decreases plasma and hepatic IL-6, TNF-α, chemokine (C-C motif) ligand 2 (CCL2), and C-reactive protein (CRP) levels in the same model when administered at a dose of 3 mg/kg per day for 28 days.
History
Ipragliflozin L-proline was approved in Japan in January 2014 for the treatment of type 2 diabetes. The drug was discovered by Astellas Pharma and co-developed and marketed with Kotobuki Pharmaceutical and Merck Sharp Dohme as Suglat?. Similar to empagliflozin (XIII), ipragliflozin L-proline is a sodium-glucose 1956 A. C. Flick et al. / Bioorg. Med. Chem. 24 (2016) 1937–1980 co-transporter-2 inhibitor which prevents glucose reabsorption by excreting excess glucose in the urine. Ipragliflozin exhibits remarkable selectivity over SLGT-1 (>250x).
Uses
Ipragliflozin is a potent and selective inhibitor of sodium-glucose cotransporter-2 (SGLT2) and can serve as a potential agent for the treatment of type 1 and type 2 diabetes.
Trade name
Suglat
Synthesis
Commercial 5-bromo-2-fluorobenzaldehyde (123) was
subjected to nucleophilic attack upon subjection to lithiated
benzo[b]thiophene (124) to afford the dibenzylic alcohol 125 in
85% yield. This alcohol was then halogenated by means of thionyl
chloride in acetonitrile to give 126, which was followed by treatment
with sodium borohydride to give rise to 2-(5-bromo-2-fluorophenyl)-
1-benzothiophene (127), which was isolated by
crystallization from 2-propanol and methanol in 81% yield across
the two steps. Bromide 127 then underwent lithium–halogen
exchange prior to exposure to 2,3,4,6-tetrakis-O-(trimethylsilyl)-
D-glucono-1,5-lactone (128) in toluene. Without workup, the
resulting mixture was treated with a solution of methanol and
HCl at 0 C to give a globally desilylated a-glucopyranoside intermediate.
Subjection to acetic anhydride and 4-dimethylaminopyridine
furnished tetra-O-acetyl ipragliflozin (129) in 75% yield for
the 3 steps. Polyacetate 129 was then saponified using aqueous
sodium hydroxide and the product was crystallized from methanol
and water and subsequently treated with D-proline in ethanol to
furnish the desired product ipragliflozin D-proline (XVI) in 68%
yield.
Mode of action
Ipragliflozin is a selective SGLT2 (sodium-glucose co-transporter 2) inhibitor discovered through research collaboration with Kotobuki Pharmaceutical Co., Ltd. SGLTs are membrane proteins that exist on the cell surface and transfer glucose into cells. SGLT2 is a subtype of the sodium-glucose co-transporters and plays a key role in the reuptake of glucose in the proximal tubule of the kidneys. Ipragliflozin reduces blood glucose levels by inhibiting the reuptake of glucose.
Check Digit Verification of cas no
The CAS Registry Mumber 761423-87-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 7,6,1,4,2 and 3 respectively; the second part has 2 digits, 8 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 761423-87:
(8*7)+(7*6)+(6*1)+(5*4)+(4*2)+(3*3)+(2*8)+(1*7)=164
164 % 10 = 4
So 761423-87-4 is a valid CAS Registry Number.
761423-87-4Relevant articles and documents
A concise and practical stereoselective synthesis of ipragliflozin L-proline
Ma, Shuai,Liu, Zhenren,Pan, Jing,Zhang, Shunli,Zhou, Weicheng
, p. 1064 - 1070 (2017)
A concise and practical stereoselective synthesis of ipragliflozin L-proline was presented starting from 2-[(5-iodo-2-fluorophenyl)methyl]-1-benzothiophene and 2,3,4,6-tetra-O-pivaloyl-α-D-glucopyranosyl bromide without catalyst via iodine–lithium–zinc exchange. The overall yield was 52% in three steps and the product purity was excellent. Two key diastereomers were prepared with efficient and direct access to the α-C-arylglucoside.
Suzuki-Miyaura coupling reaction using alpha-O-alkenyl sulfone as electrophilic reagent and application thereof
-
Paragraph 0405; 0409-0410, (2020/11/01)
The invention provides a Suzuki-Miyaura coupling reaction using alpha-O-alkenyl sulfone as an electrophilic reagent. The reaction comprises the following steps: weighing alpha-O-alkenyl sulfone, an organic boron reagent, a ligand, an alkali and a catalyst, and carrying out reacting in a solvent. The invention also provides application of the coupling reaction. According to the invention, alpha-O-alkenyl sulfone is used as the electrophilic reagent for the Suzuki-Miyaura coupling reaction, and the reaction raw material alpha-O-alkenyl sulfone is simple to prepare and stable in structure, and can overcome the defects of instability, preparation difficulty and the like when organic halide and sulfonic acid are used as electrophilic reagents for the Suzuki-Miyaura coupling reaction. Meanwhile,the reaction are mild in reaction conditions, compatible with a wide range of heterocyclic rings and various functional groups, high in yield and capable of realizing large-scale process production.Since the alpha-O-alkenyl sulfone is used as the electrophilic reagent for the Suzuki-Miyaura coupling reaction, high-yield generation of aryl glucoside and open-chain alkenyl ether can be realized, medicines for treating type 2 diabetes mellitus, namely ipragliflozin and 2-deoxyipragliflozin can also be prepared, and the application scope of the reaction is wide.
Ni-Catalyzed Suzuki-Miyaura Cross-Coupling of α-Oxo-vinylsulfones to Prepare C-Aryl Glycals and Acyclic Vinyl Ethers
Gong, Liang,Sun, Hong-Bao,Deng, Li-Fan,Zhang, Xia,Liu, Jie,Yang, Shengyong,Niu, Dawen
supporting information, p. 7680 - 7686 (2019/05/22)
We demonstrate that readily available and bench-stable α-oxo-vinylsulfones are competent electrophiles in Ni-catalyzed Suzuki-Miyaura cross-coupling reactions. The C-sulfone bond in the α-oxo-vinylsulfone motif is cleaved chemoselectively in these reactions, furnishing C-aryl glycals or acyclic vinyl ethers in high yields. These reactions proceed under mild conditions and tolerate a remarkable scope of heterocycles and functional groups. Preliminary mechanistic studies revealed the importance of an α-heteroatom in facilitating these transformations.
