83480-29-9 Usage
Uses
Used in Pharmaceutical Industry:
Voglibose is used as an anti-diabetic drug for treating diabetes. It is specifically used for lowering post-prandial blood glucose levels, thereby reducing the risk of macrovascular complications in diabetic patients.
Used in Diabetes Management:
Voglibose is used as an α-glucosidase inhibitor for the treatment of diabetes. It helps in managing carbohydrate-dependent metabolic disorders such as obesity by maintaining low plasma levels of glucose, triglyceride, and insulin.
Used in Research:
Voglibose is used to study its benefits as a protectant against ischemia-reperfusion injury through glucagon-like peptide 1 receptors and the phosphoinositide 3-kinase-Akt-endothelial nitric oxide synthase pathway.
Oral hypoglycemic agents
Voglibose is an oral hypoglycemic agents which can alleviate the postprandial hyperglycemia of diabetes patients. It is first successfully developed by the Takeda Company in Japan. It belongs to α-glucosidase inhibitor (a drug which can delay the intestinal absorption of carbohydrates to achieve hypoglycemic effect). Its mechanism of action is through inhibiting the activity of disaccharides hydrolase (α-glucosidase) which can hydrolyze disaccharide into monosaccharide inside the gut and thus delaying the digestion and absorption of sugar and further alleviating the postprandial hyperglycemia. In the assay of measuring the exhaled hydrogen of healthy adults given sucrose loading, the results have confirmed that this drug in its clinical dosage has an inhibitory effect on hyperglycemia. When normal rats are subject to oral administration, this product can inhibit the increased blood sugar level after the increased loading of starch, sucrose, glucose and maltose, while it has no inhibitory effect on the increased blood sugar after increased loading of glucose, fructose, and lactose. In vitro analysis of mechanism of action have shown that, for the maltase and sucrose obtained from the small intestine of pig and rat, this drug has a strong inhibitory effect; on the other hand, it has a relative low inhibitory effect on the pancreatic α-amylase of pig and rat and has no inhibitory effect on β-glucosidase. It has a competitive inhibitory effect on the disaccharide hydrolase of the isomaltase-sucrase complex from the rat small intestine.
It is understood that voglibose has a broad scope of application; it is not only suitable for elderly patients with diabetes, but also has significant efficacy on patients with refractory type II diabetes, patients with secondary failure of sulfonylureas, patients with combined hyperlipidemia diabetes, patients with merged cardiovascular diabetes disease as well as patients with combined hyperinsulinemia. Because this product does not stimulate the secretion of insulin, it can reduce the harmful effects of postprandial hyperinsulinemia, reducing the resistance of insulin and contributes to the prevention and treatment of metabolic syndrome such as cardiovascular complications.
Side Effects
Mechanism of occurrence of side effects of oral administration of hypoglycemic agents is generally that: when the unabsorbed carbohydrate enters into the large intestine, under the action of bacteria, it subjects to glycolysis which produces carbon dioxide, hydrogen, and organic acids. At the same time, because of the increased osmotic pressure of intestinal, water retention happen which therefore causes increased exhausting, bloating, and diarrhea. Since voglibose can selectively inhibit the activity of the disaccharide hydrolase in the intestine, further delaying the rapid digestion and absorption of carbohydrate in the upper small intestine, and thus reducing saccharide, leading to a lower incidence of adverse reactions. It is known to have the following adverse reactions:
1. The digestive system: diarrhea, loose stools, borborygumus, abdominal pain, constipation, loss of appetite, nausea, vomiting, heartburn (incidence of 0.1 to 5%), stomatitis, thirst, abnormal taste, and pneumatosis cystoides gastrointestinalis (0.1%).
2. Allergic symptoms: rash, itching, light sensitivity (incidence of 0.1% or less).
3. Liver: GOT, GPT, LDH, γ-GTP, ALP are increased (0.1% incidence).
4. The nervous system: headache, dizziness, staggering, drowsiness (0.1% incidence).
5. The blood system: anemia (incidence of 0.1 to 5%), thrombocytopenia (0.1%).
6. Other: paralysis, facial swelling, hazy eyes, fever, flu, tiredness, feeling of fatigue, hyperkalemia, rise of serum amylase, decrease of high-density lipoprotein, sweating, hair loss (incidence of 0.1%).
The above information is edited by the lookchem of Dai Xiongfeng.
Originator
Takeda (Japan)
Manufacturing Process
N-(1,3-Dihydroxy-2-propyl)valiolamine:To a solution of 2.0 g of valiol amine in 50 ml of N,N-dimethylformamide are
added 3.4 g of dihydroxyacetone, 1.5 ml of 2 N hydrochloric acid and 2.6 g of
sodium cyanoborohydride, followed by stirring at 60 to 70°C for 16 hours. The
reaction solution is concentrated under reduced pressure to distill off the N,N-
dimethylformamide as much as possible, and the residue is dissolved in 100 ml of water. The solution is made acid with 2 N hydrochloric acid, stirred for
30 to 40 minutes under ice-cooling, adjusted to pH 4.5 with 1 N sodium
hydroxide solution and subjected to column chromatography (250 ml) on
Dowex 50W x 8 (H + type) (produced by Dow Chemical of the United States of
America). After the washing with water, the elution is carried out with 0.5 N
aqueous ammonia. The eluate is concentrated under reduced pressure, and
the concentrate is chromatographed on a column (250 ml) of Amberlite CG-50
(NH 4 + type) (produced by Rohm and Haas Co. of the United States of
America), followed by the elution with water. The eluate is concentrated under
reduced pressure, and the concentrate is lyophilized to give 2.0 g of white
powder of N-(1,3-dihydroxy-2-propyl)valiol amine.Ethanol (about 60 ml) is added to the above lyophilized product (1.2 g) of N-
(1,3-dihydroxy-2-propyl)valiol amine, and the mixture is warmed for 30
minutes in a hot water bath (the bath temperature: 90-95°C), followed by
leaving on standing in a refiegerator. The resultant crystalline substance is
recovered by filtration, washed with ethanol and then dried in a desiccator
under reduced pressure. Yield of 0.95 g. MP: 162-163°C. [α] D 25 = +26.2° (c
= 1, H 2 O).
Therapeutic Function
Antidiabetic, Antiobesity
World Health Organization (WHO)
Acarbose and voglibose area-glucosidase inhibitors and delay
digestion/absorption of carbohydrates as well as improving postprandial
hyperglycaemia.
Biological Activity
Orally active α -glucosidase inhibitor (IC 50 values are 3.9 and 6.4 nM at sucrase and maltase respectively). Increases glucagon-like peptide 1 (GLP-1) secretion and decreases food consumption in ob/ob mice, and reduces plasma concentrations of glucose, triglycerides and insulin in Wistar fatty rats. Exhibits antidiabetic and antiobesity activity in vivo .
Check Digit Verification of cas no
The CAS Registry Mumber 83480-29-9 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,3,4,8 and 0 respectively; the second part has 2 digits, 2 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 83480-29:
(7*8)+(6*3)+(5*4)+(4*8)+(3*0)+(2*2)+(1*9)=139
139 % 10 = 9
So 83480-29-9 is a valid CAS Registry Number.
InChI:InChI=1/C10H21NO7/c12-2-5(3-13)11-6-1-10(18,4-14)9(17)8(16)7(6)15/h5-9,11-18H,1-4H2/t6-,7?,8+,9-,10?/m0/s1
83480-29-9Relevant articles and documents
Synthesis method of voglibose
-
, (2021/08/07)
The invention provides a synthesis method of voglibose, and solves the technical problems that in an existing synthesis method of voglibose, raw materials are difficult to obtain, high in price, large in investment, low in yield and not suitable for industrial production. The synthesis method comprises the steps: synthesizing a compound V by taking glucose monohydrate and sodium acetate as raw materials through eleven reaction steps; and preparing a compound VIII from the compound V through an addition reaction, a ring-opening reaction and an aldol condensation reaction, and thus obtaining voglibose through amination reduction of the compound VIII. The synthesis method of voglibose can be widely applied to the technical field of voglibose synthesis methods.
Method for preparing voglibose and corresponding intermediate
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Paragraph 0152-0154, (2019/01/23)
The invention relates to a novel intermediate for preparing voglibose and a preparation method of the voglibose. In particular, the intermediate is shown as a formula II as shown in the specification.The intermediate is prepared by a reaction of a compound shown as a formula I with peroxide; in addition, the intermediate can be hydrolyzed to form valiolamine; and voglibose is further synthesized.The method is simple, environmentally-friendly and high in yield.
Preparation method of voglibose
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Paragraph 0007; 0019-0022, (2019/10/22)
The invention discloses a preparation method of voglibose. The preparation method comprises the steps of adopting tetrabenzyl voltolose as a raw material for a reaction in an aprotic solvent in the presence of boron halide, and adding a basic substance for crystallization, suction filtration and recrystallization to obtain the high-purity and high-yield voglibose after the reaction is completed. The whole synthesis process has the advantages that the raw material cost is extremely low, the reaction time is short, and the product yield and the quality are high; the method is suitable for industrial production.
Preparation method for voglibose
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Paragraph 0032; 0033, (2018/11/27)
The invention discloses a preparation method for a drug namely voglibose (AO128) I for treatment of diabetes. With the preparation method provided by the invention, a target product with a yield of atleast 15% is obtained through seven steps by using an intermediate II derived from shikimic acid as a raw material. The method comprises the following steps: with a ring-opening product II as a starting raw material, allowing the ring-opening product II to undergo nucleophilic substitution with sodium azide so as to obtain a configuration-inverted intermediate III; allowing the intermediate III to react with benzoyl chloride so as to obtain a product IV; then allowing double bonds of the product IV to undergo high-selectivity catalytic oxidation through rhodium so as to obtain a diol productV; reducing an ester group of the diol product V through sodium borohydride so as to obtain a compound VI containing three hydroxyl groups; protecting the primary hydroxyl group and the secondary hydroxyl group of the compound VI so as to obtain an intermediate VII; allowing the intermediate VII to connect with dibenzoyl oxyacetone for further reduction so as to obtain a compound VIII; and removing all protecting groups from the compound VIII by one step so as to obtain a target product I, i.e., the voglibose (AO128). The preparation method provided by the invention has the advantages of cheapand easily-available raw materials and used reagents, high stereoselectivity, high yield and possibility of industrial production.
Amino sugar compound and preparation method and application thereof
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Paragraph 0060; 0068; 0069, (2017/09/13)
The invention discloses an amino sugar compound as shown in formula I, a preparation method of the amino sugar compound and application of the amino sugar compound to the preparation of a compound as shown in formula A.
Structural identification of 4-benzyl-voglibose hydrochloride monohydrate using NMR and single-crystal X-ray diffraction methods
Zhang, Fen-Fen,Zhao, Yu-Qin,Fan, Jian-Ping,Liu, Li-Gang,Li, Rui-Wen,Shen, Wen-Bin,Ding, Ya
, p. 81 - 86 (2015/02/19)
The chemical structure studies on an important related substance of voglibose have been carried out using NMR spectroscopy and single crystal X-ray crystallography. For the structure identification study, hydrochloride monohydrate of this compound was iso
Diastereospecific epoxidation and highly regioselective ring-opening of (+)-valienamine: Practical synthesis of (+)-valiolamine
Ji, Li,Zhang, Ding-Feng,Zhao, Qian,Hu, San-Ming,Qian, Chao,Chen, Xin-Zhi
, p. 7031 - 7037 (2013/07/26)
An efficient and practical synthesis of (+)-valiolamine starting from readily available aminocyclitol (+)-valienamine in five steps and up to 80% total yield in gram-scale quantities is reported. Diastereospecific epoxidation by means of substrate directable reaction and regioselective ring-opening of corresponding epoxide are the key reactions in the synthesis, which circumvent laborious purification of products using chromatographical separation. The detailed mechanisms of epoxidation and ring-opening attacked by halide, including the directing and steric hindrance effect, are also discussed.
HYPOGLYCEMIC EFFECT ENHANCER
-
, (2012/02/01)
A hypoglycemic effect enhancer for enhancing the activity of an α-glucosidase inhibitor, the enhancer comprising at least one kind of bacteria selected from the group consisting of bifidobacteria, lactic acid bacteria, saccharifying bacteria, and butyric acid bacteria.
Process for preparation of voglibose
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Page/Page column 6, (2008/06/13)
A process capable of conveniently preparing voglibose at a low cost in a safe process, and an intermediate which can be suitably used in the process and a process for preparing the intermediate are provided. An inositol derivative represented by the formula (VI): wherein Prt is a protecting group of hydroxyl group; a process for preparing the inositol derivative, wherein a cyclohexanone compound represented by the formula (IV): wherein Prt is as defined above, is dihydroxyaminated using a dihydroxyaminating agent and a reducing agent; and a process for preparing voglibose represented by the formula (VIII): wherein the inositol derivative is oxidized to give an inositol compound, and the protecting group, Prt of the inositol compound is deprotected.
PROCESSES FOR THE PURIFICATION OF VOGLIBOSE AND INTERMEDIATES THEREOF
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Page/Page column 8, (2008/06/13)
Processes for the purification of voglibose are provided. Also provided are processes for the purification of substituted or unsubstituted 5-oxo-1,2,3,4-cyclohexanetetrol and substituted 5-amino-1,2,3,4-cyclohexanetetrol, which compounds are useful intermediates in the preparation of voglibose.
