Rosiglitazone and its intermediates
Rosiglitazone
CAS: 122320-73-4
Molecular Formula: C18H19N3O3S
Rosiglitazone and its intermediates - Names and Identifiers
| Name | Rosiglitazone |
| Synonyms | AVANDIA Rosiglitazone ROSIGLITAZONE ROSIGLITAZONE HCL Rosiglitazone free base Rosiglitazone and its intermediates 5-(4-[2-(METHYL-PYRIDIN-2-YL-AMINO)-ETHOXY]-BENZYL)-THIAZOLIDINE-2,4-DIONE 5-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)-1,3-thiazolidine-2,4-dione 5-[[4-[2-(methyl-2-pyridinylamino)ethoxy]-phenyl]methyl]-2,4-thiazolidine-dione 5-[[4-[2-(Methyl-2-pyridinylamino)ethoxy]-phenyl]methyl]-2,4-thiazolidine-dione 5-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)-1,3-thiazolidine-2,4-dione hydrochloride 5-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)-1,3-thiazolidine-2,4-dione (2Z)-but-2-enedioate |
| CAS | 122320-73-4 |
| EINECS | 924-121-1 |
| InChI | InChI=1/C18H19N3O3S.ClH/c1-21(16-4-2-3-9-19-16)10-11-24-14-7-5-13(6-8-14)12-15-17(22)20-18(23)25-15;/h2-9,15H,10-12H2,1H3,(H,20,22,23);1H |
Rosiglitazone and its intermediates - Physico-chemical Properties
| Molecular Formula | C18H19N3O3S |
| Molar Mass | 357.43 |
| Density | 1.315±0.06 g/cm3(Predicted) |
| Melting Point | 153-155 C |
| Boling Point | 585.0±35.0 °C(Predicted) |
| Flash Point | 307.6°C |
| Solubility | DMSO: ≥10mg/mL |
| Vapor Presure | 1.14E-13mmHg at 25°C |
| Appearance | powder |
| Color | White to Off-White |
| Merck | 14,8265 |
| pKa | 6.34±0.50(Predicted) |
| Storage Condition | 2-8°C |
| Physical and Chemical Properties | Crystallization from methanol, melting point 153-155 °c. |
| Use | For the treatment of diabetes |
Rosiglitazone and its intermediates - Risk and Safety
| Hazard Symbols | Xi - Irritant |
| Risk Codes | 36/38 - Irritating to eyes and skin. |
| Safety Description | S26 - In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. S37/39 - Wear suitable gloves and eye/face protection |
| WGK Germany | 3 |
| RTECS | XJ5813850 |
| HS Code | 2934100000 |
Rosiglitazone and its intermediates - Reference
| Reference Show more | 1. Wu Enkai, Zhang Tingting, Peng Chunxiu, et al. Based on metabonomics, the improvement effect of Pu 'er tea brown element on metabolic syndrome in rats under swing exercise [J]. Food Science, 2019, 40(19). 2. Ning Yibo, Cheng Long, Huang Zhiqi, He Runcheng, Sun Jianning, Dong Shifen. Effect of emodin on lipid metabolism in aged mice based on fat browning [J]. Zhongnan pharmacy, 2021,19(03):478-483. 3. [if = 2.571] Rui Wei et al."anti-proliferative effect of rosiglitazone in the human t‐lymphocyte leukaemia cell line jurkat cells." cell biol int.2018 may; 42(5):515-524 4. [IF = 5.279] Jing Zhou et al."Ginsenoside F2 Suppresses Adipogenesis in 3T3-L1 Cells and Obesity in Micevia the AMPK Pathway." J Agr Food Chem. 2021;69(32):9299-9312 5. [IF = 3.498] Kangrui Yuan et al."Investigation of antidiabetic effect of a new dicarboxylic acid coordination polymer with Zn(II)." J Solid State Chem. 2021 Nov;303:122477 |
Rosiglitazone and its intermediates - Nature
Open Data Verified Data
crystallized from methanol, melting point 153-155 °c.
Last Update：2024-01-02 23:10:35
Rosiglitazone and its intermediates - Preparation Method
Open Data Verified Data
2-[N-methyl-N-di (2-pyridyl) amino] ethanol was dissolved in dimethylformamide, and sodium hydride was added in portions under the protection of nitrogen. When the vigorous reaction is slowed down, 4 fluorobenzaldehyde is added, the treated compound and 2.4 thiazolinedione are dissolved in toluene, piperidine acetate is added, reflux, and the treated compound is dissolved in dioxane, the hydrogenation was carried out at room temperature and atmospheric pressure under the action of a catalyst. The mixture was filtered, concentrated under reduced pressure and recrystallized.
Last Update：2022-01-01 09:24:06
Rosiglitazone and its intermediates - Use
Open Data Verified Data
developed by Smith Kline Beecham, UK, and first listed in the United States in September 1999 by Brist01_Myers Squibb, USA. Thiazolidinedione insulin sensitizer. For insulin resistance in patients with type II diabetes, can be combined with metformin or sulfonylurea drugs.
Last Update：2022-01-01 09:24:06
Rosiglitazone and its intermediates - Reference Information
| (IARC) carcinogen classification | 3 (Vol. 108) 2016 |
| thiazolidinediones hypoglycemic drugs | rosiglitazone and pioglitazone are currently commonly used in the clinical treatment of diabetes in my country The thiazolidinedione hypoglycemic drugs, this product is an insulin sensitizer, which can reduce blood sugar by increasing the sensitivity of skeletal muscle, liver, and adipose tissue to insulin and improving the use of glucose by cells, it can significantly reduce fasting blood glucose, insulin and C- peptide levels, and also reduce postprandial blood glucose and insulin. But the patient is required to have a certain ability to secrete insulin. It is clinically suitable for patients with type 2 diabetes who are still not satisfied with diet control and exercise, and can also be combined with biguanides or sulfonylureas for patients with poor blood sugar control when used alone. For single use, the initial oral dose is 4mg daily, and it can be increased to 8mg daily after 12 weeks if necessary. Take it on an empty stomach or during meals. Elderly patients may have mild to moderate edema and anemia after taking it, so patients with edema should use it with caution. rosiglitazone has similar adverse reactions and incidence rates with hypoglycemic drugs such as sulfonylurea and metformin, such as 9.9% incidence of upper respiratory tract infection, 7.6% trauma and 5.9% headache. In addition to the above-mentioned adverse reactions similar to other hypoglycemic drugs, rosiglitazone also has its unique adverse reactions, namely mild to severe edema caused by urinary retention and increased blood volume. This may be the reason why the drug causes cardiovascular risks. on may 21, 2007, the new england journal of medicine published online the results of a meta-analysis that rosiglitazone may increase the risk of death from heart disease in patients. On July 30, 2007, the U.S. Food and Drug Administration (FDA) held a hearing and believed that rosiglitazone had cardiovascular safety risks, but supported that the drug remained in the U.S. market. on August 14, 2007, FDA decided to add a black box warning to the risk of heart failure in the instructions of all thiazolidinediones (tzd). On November 27, 2007, the American Diabetes Association and the European Diabetes Research Association issued a joint statement to modify the instructions for the use of thiazolidinediones, stating that such drugs can increase fluid retention, congestive heart failure and fracture risk, among which rosiglitazone may increase the risk of myocardial infarction. In September 2010, F DA announced that it would strictly limit the use of drugs containing rosiglitazone, only for patients with type 2 diabetes who cannot control blood sugar by other drugs. On March 2, 2011, the FDA released information to the public about the addition of information about the cardiovascular risks (including heart attack) of the diabetes drug rosiglitazone (rosiglitazone,Avandia) in the physician's instructions and patient medication guidelines. |
| pharmacological effects | rosiglitazone achieves lasting blood sugar control by directly reducing insulin resistance and improving β cell function. It is a highly selective and potent peroxisome proliferator-activated receptor γ (PPARγ) agonist. The receptor is a protein found in adipose, skeletal and liver tissues of insulin-sensitive tissues. the absolute bioavailability of rosiglitazone is 99%. Rosiglitazone is absorbed rapidly in healthy volunteers and reaches its peak concentration at an average of 1h after taking the drug. It can increase the insulin content in the islets without affecting the secretion of insulin. Rosiglitazone prevents the reduction of β cells by reducing cell death. These evidences show that rosiglitazone has a protective effect on β cells. Rosiglitazone can reduce hyperinsulinemia and plasma free fatty acid levels. Decreased plasma insulin levels suggest that rosiglitazone reduces the burden on pancreatic beta cells. Since the high level of free fatty acids has a toxic effect on the pancreas, reducing the level of free fatty acids also has a protective effect on the function of pancreatic β cells. Therefore, the basic physiological link of type 2 diabetes is to reduce insulin resistance, improve β cell function to control blood sugar. |
| usage and dosage | the initial dose is 2~4mg, once/d. For patients who need further blood sugar control, the dose can be increased to 8mg/d. You can take it orally on an empty stomach or with food, on a meal or in divided doses. Not relying on meal time makes its application more flexible. It has good safety and tolerability and long-lasting control of blood sugar. |
| clinical application | 1 is more effective in controlling blood sugar. 493 patients with type 2 diabetes (failed diet control or previously treated) have been reported to participate. At baseline, the average fasting blood glucose was about 225mg/dl and the average HbA1c was 8.9%. After 4 weeks, patients were randomized to receive rosiglitazone 4mg/d or 8mg/d or placebo for a total of 26 weeks. Compared with placebo, rosiglitazone (4mg/d or 8mg/d) significantly reduced empty abdominal blood glucose by 58mg/dl and 76mg/dl, respectively, and HbA1c decreased by 1.2% and 1.5%, respectively. 2, significantly reduce postprandial hyperglycemia, 8 weeks to study the effect of rosiglitazone monotherapy on patients with type 2 diabetes. The results showed that the postprandial blood glucose level of patients with type 2 diabetes was significantly reduced, and the rosiglitazone 8mg/d treatment group was more obvious. It is important to demonstrate that the insulin sensitizing effect of rosiglitazone improves peripheral glucose utilization. Lowering postprandial glucose is important because long-term postprandial hyperglycemia increases the risk of myocardial infarction and mortality. 3, combined with metformin significantly reduced blood sugar. It works by increasing glucose uptake in skeletal muscle and adipose tissue and metformin in glycogen output. The results of the study confirmed that rosiglitazone combined with metformin has a complementary effect in reducing hyperglycemia. It shows that metformin plus rosiglitazone 4mg/d or 8mg/d significantly reduces fasting blood glucose and HbA1c compared with metformin alone. In addition to blood sugar control, free fatty acids were also reduced by 2.6mg/dl and 4.3mg/dl respectively from baseline. The main pathogenic mechanisms associated with metabolic abnormalities in type 2 diabetes mellitus with sulfonylurea drugs are: insulin resistance in target tissues, especially in skeletal muscle and liver, decreased abnormal glucose uptake and increased glycogen output. 4. Rosiglitazone and sulfonylurea are combined to determine the effect of a drug that reduces insulin resistance and another drug that promotes insulin secretion is better than the two drugs alone. The results confirmed that the combination of the two drugs can further improve hyperglycemia. Combination with sulfonylureas significantly reduced fasting blood glucose and HbA1c. At the same time, the level of free fatty acids was significantly reduced. 5, combined with insulin: rosiglitazone is a powerful insulin sensitizer, which can reduce the demand for endogenous insulin when blood sugar is controlled within the normal range. Fasting blood glucose and HbA1c were significantly improved. |
| adverse reactions | 1, liver damage: rosiglitazone clearance t1/2 in patients with liver disease is 2 hours longer than that in healthy people. If the patient has clinically active liver disease or increased serum transaminase, rosiglitazone should not be used. 2, renal damage: The pharmacokinetics of rosiglitazone in patients with mild renal damage or dialysis dependence is not different from that in patients with normal renal function. 3, hypoglycemia: When treated with sulfonylurea drugs, there may be a risk of hypoglycemia, so the dose of rosiglitazone should be in a small dose. 4, a small number of patients with anemia and edema. As with other thiazolidinediones, when rosiglitazone alone or in combination with other drugs, hemoglobin and hematocrit decreased slightly from baseline ( 5, respectively. The frequency of arrhythmia in rosiglitazone-treated patients was similar to or lower than that of metformin and sulfonylurea. No changes in cardiac structure or function were observed by echocardiography. 6. Clinical trials of rosiglitazone combined with other drugs, including β-blockers, ACE inhibitors, calcium channel blockers, lipid-lowering agents, diuretics, estrogen, salicylic acid, paracetamol and other steroidal antipyretic analgesics. Rosiglitazone is well tolerated in combination with these drugs, and no clinically significant drug interactions have been found. 7, with slight weight gain, 4mg/d or 8mg/d for more than 52W, with an average weight gain of 1.75kg or 2.5kg. Similar to other hypoglycemic drugs. This is consistent with an improvement in glycemic control. |
| precautions | those who are allergic to the ingredients in this product are prohibited. This product is not suitable for patients with type I diabetes or diabetic ketoacidosis. For premenopausal and anovulatory women with insulin resistance, ovulation can be resumed with the improvement of insulin sensitivity. Contraception should be paid attention. Patients with severe cardiac insufficiency are not recommended to use this product. Liver function should be tested regularly during medication. Patients with slightly elevated ALT should be used with caution. If ALT is 3 times greater than normal or there are abnormal symptoms of liver function or jaundice, the drug should be stopped. There is no information about patients under 18 years old taking this product, so it is not recommended. |
| use | thiazolidinedione insulin sensitizer. It is suitable for the treatment of non-insulin-dependent (type II) diabetes. for the treatment of diabetes |
| production method | 8.9g 2-(N-methyl-N-(2-pyridyl) amino) ethanol is dissolved in 60ml of dimethylformamide, and 0.7g of 60% sodium hydride is added in batches under the protection of nitrogen. When the violent reaction slows down, 2.9g of 4-fluorobenzaldehyde is added and heated at 80 ℃ for 16h. Cool and add 400ml of water. Extract with 3 × 250ml ether, combine the extracts, wash with 2 × 100ml salt, dry, filter, concentrate to dry, and obtain compound (I). 3.2g of compound (I) and 1.1g of 2, 4-thiazoline diketone were dissolved in 100ml of toluene, and the catalytic amount of piperidine acetate was added and refluxed for 2h. Cooling and filtering to obtain compound (II) with a melting point of 177-190 ℃. Compound (II) is dissolved in dioxane and hydrogenated at room temperature and normal pressure under 10% Pd-C catalysis until hydrogen absorption stops. Filter, concentrate under reduced pressure to dry. The residue was recrystallized with methanol to obtain roglisone with a melting point of 153~155 ℃. |
| toxic substance data | information provided by: pubchem.ncbi.nlm.nih.gov (external link) |
Last Update：2024-04-09 20:52:54
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Tel: 0714-3999186
Email: 2853786052@qq.com
Mobile: 86+15671228036
QQ: 2853786052
Wechat: 15671228036
Multiple SpecificationsSpot supply
Product Name: Rosiglitazone Visit Supplier Webpage Request for quotationCAS: 122320-73-4
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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