Rosuvastatin

Base Information

• Chemical Name: Rosuvastatin
• CAS No.: 287714-41-4
• Deprecated CAS: 1354641-86-3
• Molecular Formula: C22H28FN3O6S
• Molecular Weight: 481.545
• European Community (EC) Number: 689-191-5
• UNII: 413KH5ZJ73
• DSSTox Substance ID: DTXSID8048492
• Nikkaji Number: J3.118.169K
• Wikipedia: Rosuvastatin
• Wikidata: Q415159
• NCI Thesaurus Code: C66523
• RXCUI: 301542
• Pharos Ligand ID: WKJ4M7B51M5V
• Metabolomics Workbench ID: 43328
• ChEMBL ID: CHEMBL1496
• Mol file: 287714-41-4.mol

Synonyms:Calcium, Rosuvastatin;Crestor;rosuvastatin;rosuvastatin calcium;ZD 4522;ZD4522

Chemical Property of Rosuvastatin

Chemical Property:

• Vapor Pressure: 2.38E-23mmHg at 25°C
• Melting Point: 161.9 °C
• Refractive Index: 1.597
• Boiling Point: 745.6 °C at 760 mmHg
• PKA: 4.25±0.10(Predicted)
• Flash Point: 404.7 °C
• PSA: 149.30000
• Density: 1.368 g/cm³
• LogP: 3.48250
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility.: DMSO (Slightly), Methanol (Slightly), Water (Slightly)
• XLogP3: 1.6
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 10
• Rotatable Bond Count: 10
• Exact Mass: 481.16828496
• Heavy Atom Count: 33
• Complexity: 767

Purity/Quality:

99%, ^*data from raw suppliers

Rosuvastatin-13C,D3sodium ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antilipemic Agents
• Canonical SMILES: CC(C)C1=NC(=NC(=C1C=CC(CC(CC(=O)O)O)O)C2=CC=C(C=C2)F)N(C)S(=O)(=O)C
• Isomeric SMILES: CC(C)C1=NC(=NC(=C1/C=C/[C@H](C[C@H](CC(=O)O)O)O)C2=CC=C(C=C2)F)N(C)S(=O)(=O)C
• Recent ClinicalTrials: A Phase 1 Study to Evaluate the Potential Drug Interactions Between Repotrectinib and Metformin, Digoxin, and Rosuvastatin in Patients With Advanced Solid Tumors
• Recent EU Clinical Trials: POESIA Study: Pleiotropic effects of PCSK 9 inhibition and bempedoic acid - Changes in Platelet Function and Inflammation Markers
• Recent NIPH Clinical Trials: Clinical pharmacology study to evaluate the drug-drug interactions of TAS-115 in healthy subjects
• Description: Known as an antilipemic agent, rosuvastatin belongs to the class of medications called statins, which is primarily used in the treatment of dyslipidemia, including high cholesterol and related conditions. It functions by blocking the enzyme that helps make cholesterol in the body, which is effective to improve cholesterol levels by reducing blood total cholesterol and triglyceride levels while raising the good cholesterol, HDL cholesterol levels in combination with a healthy diet and exercise program. It is also applied to treat people with certain inherited cholesterol disorders. Besides, since the high level of cholesterol is related to angiocardiopathy, rosuvastatin is beneficial to prevent people from cardiovascular diseases, which is used to reduce the risk of heart attacks, stroke, and angioplasty for people who have at least 2 risk factors for cardiovascular disease. Rosuvastatin is the most recent FDA-approved statin (doses 5–40 mg) for the treatment of dyslipidemia. Rosuvastatin, which has a structure similar to other synthetic statins, has a long halflife (20–24 hours) similar to atorvastatin and hydrophilicity comparable to pravastatin. Consequently, rosuvastatin is minimally metabolized and has no significant cytochrome P450 drug interactions. The efficacy of rosuvastatin is superior to that of other statins. Compared to atorvastatin, rosuvastatin provides approximately an 8% additional lowering of LDL-C on an equivalent dose level. This provides modestly more efficacy than a doubling of the dose of atorvastatin. Rosuvastatin also increases HDL-C slightly more than atorvastatin, especially at the highest doses.
• Drug Interactions: Cyclosporine: In combined usage, the AUC of Rosuvastatin is 7 times higher than that seen in healthy volunteers (using the same dosage). Co-administration does not affect cyclosporine plasma concentration. Vitamin K antagonists: As with other HMG-CoA reductase inhibitors, starting Rosuvastatin or gradually increasing dosage may increase International Normalized Ratio (INR) in patients simultaneously using vitamin K antagonists (such as Warfarin). Discontinuing use or gradually reducing dosage reduces INR. In this case, proper testing of INR is required. Combined administration of iferrate, fenofibrate, other fibrates, and lipid lowering dosages (≥1g/日) of niacin with HMG-CoA reductase inhibitors increases the risk of myopathy, possibly because their individual administration can also cause myopathy. Antacids: Combined administration with antacids containing aluminum magnesium hydroxide can reduce Rosuvastatin plasma levels by about 50%. This affect may be alleviated if the antacid is administered 2 hours later. The clinical significance of this drug interaction has not yet been studied. Erythromycin: Combined administration reduces AUC (0-t) of Rosuvastatin by 20%, and Cmax by 30%. This interaction may be caused by an increase in gastrointestinal motility caused by erythromycin. Oral contraceptives/Hormone Replacement Therapy (HRT): Administration combined with oral contraceptives increased ethinyl estradiol and norethindrone AUC by 26% and 34% respectively. These plasma concentrations should be considered when choosing dosages of oral contraceptives. There is no pharmacokinetic data for subjects who use this product with HRT, so the presence of similar interactions cannot be ruled out. In clinical trials, however, this combination is widespread and well tolerated.
• Uses: Rosuvastatin Calcium is a competitive inhibitor of HMG-CoA reductase with IC50 of 11 nM.
• Clinical Use: HMG CoA reductase inhibitor: Hyperlipidaemia
• Drug interactions: Potentially hazardous interactions with other drugs Anti-arrhythmics: concentration possibly increased by dronedarone - reduce dose of rosuvastatin. Antibacterials: erythromycin reduces concentration of rosuvastatin; increased risk of myopathy with daptomycin and fusidic acid - avoid. Anticoagulants: effect of coumarins and phenindione enhanced. Antifungals: concentration increased by itraconazole - reduce dose of rosuvastatin. Antivirals: increased risk of myopathy with atazanavir, darunavir, dasabuvir, fosamprenavir, indinavir, ledipasvir, lopinavir, paritaprevir, ritonavir, saquinavir and tipranavir - reduce dose of rosuvastatin, avoid with fosamprenavir, indinavir, ledipasvir, ritonavir and saquinavir. Ciclosporin: increased risk of myopathy - avoid. Clopidogrel: concentration of rosuvastatin increased, maximum rosuvastatin dose is 20 mg in normal renal function. Colchicine: possible increased risk of myopathy. Cytotoxics: concentration increased by eltrombopag - reduce dose of rosuvastatin. Lipid-lowering agents: increased risk of myopathy with ezetimibe, fibrates, gemfibrozil (avoid) and nicotinic acid - reduce dose of rosuvastatin. Teriflunomide: concentration increased by teriflunomide - reduce dose of rosuvastatin.

Technology Process of Rosuvastatin

There total 35 articles about Rosuvastatin which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 81.0%

tert-butyl-6-[(1E)-2-[4-(4-fluorophenyl)-6-(1-methylethyl)-2-[methyl(methylsulfonyl)amino]-5-pyrimidinyl]ethenyl]-2,2-dimethyl-1,3-dioxane-4-acetate (1007871-85-3,1378943-63-5) → rosuvastatin (287714-41-4)

Guidance literature:

With hydrogenchloride; water; In tetrahydrofuran; at 80 ℃; for 2h; Product distribution / selectivity;

Reference yield:

rosuvastatin methylamine salt (355805-96-8) → rosuvastatin (287714-41-4)

Guidance literature:

With hydrogenchloride; In water; ethyl acetate; at 25 - 30 ℃; pH=4.0;

Reference yield:

methyl (3R,6E)-7-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamido)-6-(propan-2-yl)pyrimidin-5-yl]-3-hydroxy-5-oxohept-6-enoate (147118-39-6) → rosuvastatin (287714-41-4)

Guidance literature:

methyl (3R,6E)-7-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamido)-6-(propan-2-yl)pyrimidin-5-yl]-3-hydroxy-5-oxohept-6-enoate; With diethyl methoxy borane; In tetrahydrofuran; methanol; at -100 - -98 ℃; for 1.5h;

With sodium tetrahydroborate; In tetrahydrofuran; methanol; at -100 ℃; for 1h;

With water; sodium hydrogencarbonate; acetic acid; more than 3 stages;

upstream raw materials:

(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid methyl ester

(3R,5S,6E)-7-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamido)-6-(isopropyl)pyrimidine-5-yl]-3,5-dihydroxyhept-6-enoic acid isopropylamine

rosuvastatin tert-butyl ester

rosuvastatin methylamine salt

Downstream raw materials:

(+)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]-(3R,5S)-dihydroxy-(E)-heptenoic acid cyclohexylammonium salt

(3R,5S,6E)-7-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamido)-6-(isopropyl)pyrimidine-5-yl]-3,5-dihydroxyhept-6-enoic acid isopropylamine

(+)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]-(3R,5S)-dihydroxy-(E)-heptenoic acid tert-octylammonium salt

dehydroabietylamine salt of rosuvastatin

Refernces

• 1、 -. "Method for preparing rosuvastatin and pitavastatin 2, 5-diene heptanoate compound". Paragraph 0027-0030. . Retrieved 2020/05/14.
• 2、 -. "Purification method of rosuvastatin calcium key intermediate". Paragraph 0053-0055. . Retrieved 2019/05/08.