287714-41-4 Usage
Uses
Used in Pharmaceutical Industry:
Rosuvastatin is used as an antilipemic agent for the treatment of dyslipidemia, including high cholesterol and related conditions. It helps improve cholesterol levels by reducing blood total cholesterol and triglyceride levels while raising HDL cholesterol levels, in combination with a healthy diet and exercise program.
Used in Cardiovascular Disease Prevention:
Rosuvastatin is used as a cardioprotective agent to reduce the risk of heart attacks, stroke, and angioplasty in people with at least two risk factors for cardiovascular disease. Its long half-life and minimal metabolism make it a preferred choice for patients requiring long-term cholesterol management.
Used in Research and Development:
Rosuvastatin is used as a competitive inhibitor of HMG-CoA reductase in research settings, with an IC50 of 11 nM. This property makes it a valuable tool for studying the effects of cholesterol synthesis inhibition on various biological processes and for developing new therapeutic strategies for dyslipidemia and related conditions.
Used in Drug Delivery Systems:
Rosuvastatin's long half-life and hydrophilicity make it a suitable candidate for incorporation into novel drug delivery systems. These systems aim to enhance the drug's bioavailability, delivery, and therapeutic outcomes, particularly in the treatment of dyslipidemia and cardiovascular diseases.
Indications and Usage
Rosuvastatin is a drug against hyperlipidemia, a HMG-CoA reductase inhibitor, successfully developed by British AstraZeneca. Applicable to treat a variety of lipid abnormalities, including primary hypercholesterolemia, mixed lipid abnormalities, simple hypertriglyceridemia, and senile coronary heart disease complicated by hyperlipidemia. Rosuvastatin is currently the statin with the strongest and most comprehensive lipid-lowering effect on the market, reducing LDL cholesterol and improve HDL function better than the world-recognized leader atorvastatin, and with better tolerability, fewer side effects, and unique pharmacokinetic effects.
Mechanisms of Action
Rosuvastatin is a selective inhibitor of methylglutaryl coenzyme A reductase (HMG-CoA). The HMG-CoA reductase inhibitor is a rate-limiting enzyme which transforms 3-hydroxy-3-methylglutaryl coenzyme A into a methylpentate-cholesterol precursors. Its main site of action is the liver, reducing cholesterol in its target organ. It can competitively inhibit HMG-CoA in the liver to better reduce fat. It can also effectively promote the transfer of LDL into cells, thus enhancing the clearance of low-density lipoprotein, effectively reducing it. In addition, it can also inhibit platelet aggregation, reducing the body's inflammatory response, and protecting the function of endothelial cells, effectively stabilizing the plaque of coronary heart disease patients and reducing its effects. It increases the number of liver cell surface LDL receptors, promoting its absorption and catabolism, inhibiting hepatic synthesis of VLDL, thereby reducing the total count of VLDL and LDL particles.
For patients with homozygous and heterozygous familial and nonfamilial hypercholesterolemia or mixed dyslipidemia, it can reduce total cholesterol, LDL-C, ApoB, and non-HDL-C levels. It can also reduce TG levels and increase HDL-C levels. For patients with simple hypertriglyceridemia, Rosuvastatin can reduce total cholesterol, LDL-C, VLDL-C, ApoB, non HDL-C, and TG levels, and increase HDL-C levels.
Pharmacokinetics
Large liver uptake of orally administered Rosuvastatin, distribution volume around 134 L, and serum concentration peaks after 3-5 hours. Absolute bioavailability is 20%. Plasma protein binding rate (mainly albumin) is about 90%. Approximately 90% of the dose is excreted from feces (including absorbed and unabsorbed active substance) in the original form, with the rest discharged through urine. About 5% in the urine is in original form. Plasma clearance half-life is approximately 19 hours. Clearance half-life does not increase with dosage. The geometric mean of plasma clearance is about 50L/hour (coefficient of variation is 21.7%). As with other HMG-CoA reductase inhibitors, liver uptake of Rosuvastatin involves membrane transporter OATP-C, which is important for the removal of Rosuvastatin from the liver.
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.
Adverse Effects
Adverse reactions are usually mild and transient. Headaches, dizziness, constipation, nausea, abdominal pain, myalgia, and weakness are frequently observed.
Dosage-related elevation of creatine kinase (CK) was observed in patients taking Rosuvastatin; most cases were mild, asymptomatic, and transient. If CK levels increase (>5×ULN), treatment should be discontinued.
Effects on the liver: a dose-dependent increase of transaminase was observed in a small number of patients taking Rosuvastatin; most cases were mild, asymptomatic, and transient.
References
https://en.wikipedia.org/wiki/Rosuvastatin
http://www.medicinenet.com/rosuvastatin/article.htm
http://bodyandhealth.canada.com/drug/getdrug/apo-rosuvastatin
https://www.drugbank.ca/drugs/DB01098
Preparation
Rosuvastatin synthesis: Reduction to the 5-hydroxymethyl derivative proceeds smoothly with diisobutylaluminum hydride (DIBALH) in toluene at -10 °C. The hydroxymethyl group is then converted to the bromo derivative, which upon reaction with triphenylphosphine affords the Wittig reagent. The latter is treated with tert-butyl 2-[(4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate and provides the protected rosuvastatin ester. Removal of the dioxane protecting group by HCl, ester hydrolysis with NaOH and precipitation with CaCl2 gives rosuvastatin.Kleemann A; Cardiovascular Drugs. Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2017). NY, NY: John Wiley & Sons. Online Posting Date: January 15, 2008
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.
Metabolism
Rosuvastatin undergoes limited metabolism in the liver
mainly by the cytochrome P450 isoenzyme CYP2C9
(approximately 10%).
Approximately 90% of the rosuvastatin dose is excreted
unchanged in the faeces (consisting of absorbed and
non-absorbed active substance) and the remaining part is
excreted in urine.
Check Digit Verification of cas no
The CAS Registry Mumber 287714-41-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,8,7,7,1 and 4 respectively; the second part has 2 digits, 4 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 287714-41:
(8*2)+(7*8)+(6*7)+(5*7)+(4*1)+(3*4)+(2*4)+(1*1)=174
174 % 10 = 4
So 287714-41-4 is a valid CAS Registry Number.
InChI:InChI=1/C22H28FN3O6S/c1-13(2)20-18(10-9-16(27)11-17(28)12-19(29)30)21(14-5-7-15(23)8-6-14)25-22(24-20)26(3)33(4,31)32/h5-10,13,16-17,27-28H,11-12H2,1-4H3,(H,29,30)/b10-9+/t16-,17+/m0/s1
287714-41-4Relevant articles and documents
Preparation method of rosuvastatin calcium
-
, (2020/06/17)
The invention belongs to the technical field of medicinal chemistry, and particularly relates to a preparation method of rosuvastatin calcium. The preparation method comprises steps: in an inert atmosphere protection environment, a specific compound is used as a raw material and is reacted under the action of a dilute acid reagent to obtain a hydroxyl protecting group-removed compound; esterolysisis carried out under the action of an alkaline reagent to obtain rosuvastatin sodium; and concentrating is carried out, a proper amount of water is added, the pH value is adjusted to 3-4 by using anacid, extracting is carried out, an obtained organic layer is cooled and crystallized to obtain a rosuvastatin white solid, the white solid is dissolved in pure water, the pH value is adjusted to 8-9by using an alkali, and reacting with a calcium salt aqueous solution is carried out to obtain rosuvastatin calcium with the purity of 99.5% or above and the impurity content of less than 0.1%.
Method for preparing rosuvastatin and pitavastatin 2, 5-diene heptanoate compound
-
Paragraph 0027-0030, (2020/05/14)
The invention discloses a method for preparing rosuvastatin and pitavastatin 2, 5-diene heptanoate compound. (4R, 6S)-6-[(1E)-2-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl (methanesulfonyl)amino]-5-pyrimidine] vinyl]-2,2-dimethyl-1,3-dioxane-4-tert-butyl acetate and (4R, 6S)-6-[[(1E)-2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl] vinyl]-2, 2-dimethyl-1, 3-dioxane-4-tert-butyl acetate are respectivelytaken as starting materials of rosuvastatin and pitavastatin, deprotection and a hydrolyzation one-step method is adopted to prepare statin acid, then the statin acid is taken as a reaction substratefor dehydration and substitution two-step reaction to prepare the 2, 5-diene heptanoate compound. The preparation and synthesis routes of rosuvastatin and pitavastatin 2, 5-diene heptanoate involved in the invention are short and feasible, the operation is simple and convenient, the product yield is high, and the rosuvastatin and pitavastatin 2, 5-diene heptanoate is more suitable for large-scaleindustrial production.
Rosuvastatin calcium impurity and method for controlling quality of rosuvastatin calcium
-
, (2019/06/30)
The invention provides a rosuvastatin calcium unknown impurity and a preparation method thereof, and further provides a method for controlling the content of the rosuvastatin calcium impurity. According to the method for controlling the content of the rosuvastatin calcium impurity, the content of the impurity is controlled by controlling the content of a compound shown in formula (RC) in an R1 compound. The invention further provides a method for controlling the quality of rosuvastatin calcium by controlling the content of the rosuvastatin calcium impurity.
PROCESS FOR MANUFACTURE OF ROSUVASTATIN CALCIUM AMORPHOUS
-
, (2019/01/22)
Disclosed here is a process for the preparation of amorphous Rosuvastatin calcium hydrate with high purity.
Purification method of rosuvastatin calcium key intermediate
-
, (2019/05/08)
The invention provides a purification method of a rosuvastatin calcium intermediate. The rosuvastatin calcium intermediate has a structure of a compound (4). The purification method comprises following steps: adding an alcohol solvent and water into a crude product containing the compound (4), then adding an ether solvent, cooling, and crystallizing to obtain the compound (4). The structure of thecompound (4) is represented in the description. The provided purification method has the advantages of simple operation, high yield, and good selectivity, can obtain high purity rosuvastatin calciumkey intermediate, which is used to prepare high quality rosuvastatin calcium, and improves the drug quality.
Ruishufatatinggan and wherein the intermediate preparation method (by machine translation)
-
, (2017/01/31)
This invention involves a kind of Ruishufatatinggan and wherein the intermediate preparation method. In particular, the invention discloses used for preparing rosuvastatin calcium and its method for preparing intermediate compounds, the structure of the specification are as intermediates for Chinese II, formula III, formula IV, formula VI or formula VII is shown in. The invention also discloses switzerland extends down his sandbank or its salt preparation method, the method is based on the aforesaid five intermediate compound and its preparation method, the operation is simple, safe, and the production cost is low, is suitable for industrial production. (by machine translation)
PROCESSES FOR THE PREPARATION OF ROSUVASTATIN OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
-
, (2016/09/22)
The present invention relates to processes for the preparation of rosuvastatin calcium of formula I and pharmaceutically acceptable salts thereof using novel intermediates, and to a pharmaceutical composition containing the same.
A he rosuvastain sandbank amino acid salt and its preparation method and application
-
Paragraph 0099-0103, (2017/01/31)
The invention relates to a rosuvastatin amino acid salt as well as a preparation method of the rosuvastatin amino acid salt. Such a compound, namely, amino acid salt, is prepared through the reaction between rosuvastatin acid and basic amino acid. The preparation method comprises the following steps of: (1) weighing rosuvastatin acid, and dissolving into C1-C6 alcohol solvents, water or a halohydrocarbon solution to obtain a solution A; (2) weighing basic amino acid, and dissolving into C1-C6 alcohol solvents or water to obtain a solution B; (3) adding the solution B to the solution A, stirring and remaining overnight, cooling the reaction liquid to reach room temperature, and then vaporizing and eliminating the solvents; (4) adding methanol, separating and filtering to remove excessive basic amino acid; and (5) concentrating, refluxing, cooling, filtering and drying to obtain the amino acid salt of the rosuvastatin. The rosuvastatin amino acid salt prepared by the preparation method not only has the effect of treating high cholesterol blood lipid and combined hyperlipidemia, and also gains the function of amino acid, thus the salt effectively fills in gaps due to the known side effects of hurt of calcium salt, sylvite and sodium salt and the like to the liver.
Process for the preparation of (E)-tert-butyl-2-(6-(2-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl,methylsulfonamido)pyrimidin-5-yl)vinyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate as a rosuvastatine intermediate
-
, (2016/12/26)
The present invention relates to a method for manufacturing (E)-tert-butyl-2-(6-(2-(4-(4-fluorophenyl)-6-isopropy l-2-(N-methyl,methylsulfonamido)pyrimidin-5-yl)vinyl)-2,2-dimethyl-1,3-dioxan-4-yl) acetate as rosubastatine intermediate that is frequently used for treating hyperlipidemia. According to the method for manufacturing in the present invention, (E)-tert-butyl-2-(6-(2-(4-(4-fluorophenyl)-6-isopropy-2-(N-methyl,methylsulfonamido)pyrimidin-5-yl)vinyl)-2,2-dimethyl-1,3-dioxan-4-yl) acetate as a rosubastatine intermediate made of solid with high and consistent purity can be mass-produced by using t-butyl 2-((4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4yl) acetate having optical activation in the form of solid with high purity.
PROCESS FOR THE PREPARATION OF STATINS IN THE PRESENCE OF BASE
-
Paragraph 0041, (2013/11/19)
The present invention relates to a process for the preparation of statins by means of a Julia-Kocienski reaction between an aldehyde and a sulfone derivative in the presence of an alkaline metal alkoxy base. The resulting derivatives are suitable as building blocks for statin type compounds such as cerivastatin, fluvastatin, pitavastatin and rosuvastatin.
