747-36-4

Usage

Chemical Properties

White Cyrstalline Solid

Uses

Different sources of media describe the Uses of 747-36-4 differently. You can refer to the following data:
1. Hydroxychloroquine Sulfate can be used as a pharmaceutical secondary standard for the determination of the analyte in pharmaceutical formulations, and biological samples by various analytical techniques.These Secondary Standards are qualified as Certified Reference Materials. These are suitable for use in several analytical applications including but not limited to pharma release testing, pharma method development for qualitative and quantitative analyses, food and beverage quality control testing, and other calibration requirements.
2. antimalarial, lupus suppressant

General Description

Hydroxychloroquine Sulfate (Hydroxychloroquine Sulphate) is a salt of hydroxychloroquine (HCQ, Plaquenil), a 4-aminoquinoline based antiviral drug.Pharmaceutical secondary standards for application in quality control provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards.

Biochem/physiol Actions

Hydroxychloroquine sulfate is an anti-inflammatory (via TNF), disease-modifying antirheumatic drug (DMARD), and a heme polymerase inhibitor. It is used in treating malaria.

Pharmacology

Antimalarial action: Hydroxychloroquine binds to DNA, interfering with protein synthesis. It also inhibits DNA and RNA polymerases. It’s active against asexual erythrocytic forms of Plasmodium malariae, P. ovale, P. vivax, and many strains of P. falciparum. Amebicidal action: Mechanism of action is unknown. Anti-inflammatory action: Mechanism of action is unknown. Drug may antagonize histamine and serotonin and inhibit prostaglandin effects by inhibiting conversion of arachidonic acid to prostaglandin F2; it may also inhibit chemotaxis of polymorphonuclear leukocytes, macrophages, and eosinophils.

Pharmacokinetics

Absorption: Absorbed readily and almost completely. Distribution: Bound to plasma proteins. It’s concentrated in the liver, spleen, kidneys, heart, and brain and is strongly bound in melanin-containing cells. Metabolism: Metabolized by the liver to desethylchloroquine and desethyl hydroxychloroquine. Excretion: Most of an administered dose is excreted unchanged in urine. Drug and its metabolites are excreted slowly in urine; unabsorbed drug is excreted in feces. Small amounts of drug may be present in urine for months after it’s discontinued. Drug appears in breast milk.

Clinical Use

Hydroxychloroquine sulfate is highly water soluble and exists in two different forms of different melting points. It is readily absorbed on oral administration, reaching peak plasma levels within 1 to 3 hours. It concentrates in organs such as the liver, spleen, kidneys, heart, lung, and brain, thereby prolonging elimination. Hydroxychloroquine is metabolized by N-dealkylation of the tertiary amines, followed by oxidative deamination of the resulting primary amine to the carboxylic acid derivative. In addition to possessing corneal and renal toxicity, hydroxychloroquine also may cause CNS, neuromuscular, GI, and hematological side effects. Hydroxychloroquine sulfate is indicated for the treatment of rheumatoid arthritis, lupus erythematosus, and malaria.

Side effects

In addition to possessing corneal and renal toxicity, hydroxychloroquine also may cause CNS, neuromuscular, GI, and hematological side effects. Hydroxychloroquine sulfate is indicated for the treatment of rheumatoid arthritis, lupus erythematosus, and malaria

Overdosage

Symptoms of drug overdose may appear within 30 minutes after ingestion and may include headache, drowsiness, visual changes, CV collapse, and seizures followed by respiratory and cardiac arrest. Treatment is symptomatic. Empty stomach by emesis or lavage. After lavage, activated charcoal in an amount at least five times the estimated amount of drug ingested may be helpful if given within 30 minutes of ingestion. Ultra-short-acting barbiturates may help control seizures. Intubation may become necessary. Peritoneal dialysis and exchange transfusions may also be useful. Forced fluids and acidification of the urine are helpful after the acute phase.

Drug interactions

Anti-arrhythmics: increased risk of ventricular arrhythmias when hydroxychloroquine administered with amiodarone – avoid concomitant use Digoxin: Hydroxychloroquine sulfate has been reported to increase plasma digoxin levels: serum digoxin levels should be closely monitored in patients receiving concomitant therapy. Antibacterials: increased risk of ventricular arrhythmias when hydroxychloroquine administered with moxifloxacin – avoid concomitant use. Ciclosporin: hydroxychloroquine increases plasma concentration of ciclosporin (increased risk of toxicity) . Antacids: as with chloroquine, antacids may reduce absorption of hydroxychloroquine so it is advised that a 4 hour interval be observed between hydroxychloroquine and antacid dosaging. Antidiabetic medicines: As hydroxychloroquine may enhance the effects of hypoglycaemic treatment, a decrease in doses of insulin or antidiabetic drugs may be required. Tamoxifen: may enhance the adverse/toxic effect of Hydroxychloroquine. Specifically, concomitant use of tamoxifen and hydroxychloroquine may increase the risk of retinal toxicity.

Metabolism

Hydroxychloroquine is metabolised to chloroquine, which in turn is extensively metabolised in the liver, mainly to monodesethylchloroquine with smaller amounts of bisdesethylchloroquine (didesethylchloroquinine) and other metabolites being formed. Monodesethylchloroquine has been reported to have some activity against Plasmodium falciparum. Chloroquine and its metabolites are excreted in the urine, with about half of a dose appearing as unchanged drug and about 10% as the monodesethyl metabolite.

InChI:InChI=1/C18H26ClN3O/c1-3-22(11-12-23)10-4-5-14(2)21-17-8-9-20-18-13-15(19)6-7-16(17)18/h6-9,13-14,23H,3-5,10-12H2,1-2H3,(H,20,21)/p+2/t14-/m0/s1

Upstream product

• 86-98-6 4,7-dichloroquinoline 
• 159346-86-8 R(-)-5--2-pentanamine 
• 137433-23-9 (R)-Hydroxychloroquine 
• 69559-11-1 rac-5--2-pentanamine 
• 155204-10-7 S(+)-5--2-pentanamine 
• 137433-23-9 (S)-Hydroxychloroquine 
• 118-42-3 hydroxychloroquine 

Relevant academic research and scientific papers

Synthesis and evaluation of enantiomers of hydroxychloroquine against SARS-CoV-2 in vitro

Since the end of 2019, the outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has evolved into a global pandemic. There is an urgent need for effective and low-toxic antiviral drugs to remedy Remdesivir's limitation. Hydroxychloroqui

An asymmetric synthesis method of optically pure (R)/(S)-hydroxychloroquine side chains

The present invention provides an optically pure (R)/ (S) - hydroxychloroquine synthesis method, using a splitting reagent to (±) -2- [(4-aminopentyl)ethylamine] ethanol is split, and recrystallization purification, purified to give optically pure (R) / (S)-2- [(4-aminopentyl) ethylamine] ethanol, the resulting single configuration of hydroxychloroquine side chain and 4,7-dichloroquinoline reaction directly to obtain a single configuration of hydroxychloroquine sulfate. The method has a simple route, easy to obtain raw materials, high yield, good three-dimensional selectivity (ee% >99%), simple operation and green environmental protection, suitable for large-scale scale production.

Preparation method of hydroxychloroquine

The invention relates to a preparation method of hydroxychloroquine, which comprises the following steps: protecting hydroxyl of 5-(N-ethyl-N-ethoxyl)-2-aminopentane through a silanization reagent, removing amino protons from tetrahydrofuran or toluene by using a bis(trimethylsilyl lithium amide) solution to form amino anions, and carrying out a substitution reaction with 4.7 dichloroquinoline to generate hydroxychloroquine. The hydroxychloroquine and sulfuric acid are salified in an alcoholic solution to generate hydroxychloroquine sulfate, and the hydroxychloroquine sulfate preparation method provided by the invention has the characteristics of low toxicity, low pollution, high purity, low reaction temperature, short reaction time, high yield and the like, and is suitable for industrialization.

Hydroxychloroquine sulfate crystal form B and preparation method thereof

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a hydroxychloroquine sulfate crystal form B and a preparation method thereof, and XRD and DSC are usedfor characterization. The hydroxychloroquine sulfate crystal form B provided by the invention is simple in preparation method, low in hygroscopicity, good in stability, capable of forming a regular crystal form and higher in solubility, thereby being beneficial to process treatment of medicines, improvement of physical and chemical properties and improvement of patent medicine properties.

Hydroxychloroquine sulfate and preparation method thereof

The invention discloses hydroxychloroquine sulfate and a preparation method thereof, and relates to the technical field of medicinal chemistry. The preparation method comprises the steps of mixing 4, 7-dichloroquinoline with a hydroxychloroquine side chain, carrying out heating condensation in the presence of an organic base catalyst, adding water and liquid, and carrying out cooling crystallization to obtain hydroxychloroquine; and dissolving hydroxychloroquine in an ethyl acetate and ethanol aqueous solution, heating, dissolving and clarifying, dropwise adding concentrated sulfuric acid, cooling, crystallizing, filtering and drying to obtain hydroxychloroquine sulfate. The method has the beneficial effects that a solvent-free reaction is used, and a catalyst is added, so that high pollution is avoided, the reaction process is accelerated, and the operation is simple; and meanwhile, the HPLC purity of the obtained hydroxychloroquine refined product is not less than 96.50%, the maximum single impurity content is less than 0.10%, the yield can reach 85%, the HPLC purity of hydroxychloroquine sulfate is not less than 98.00%, the maximum single impurity content is less than 0.10%, and the yield can reach 90%.

Preparation method of hydroxychloroquine sulfate

The invention provides a preparation method of hydroxychloroquine sulfate, specifically a preparation method of hydroxychloroquine sulfate. The method comprises the following steps: (1) preparation of hydroxychloroquine: (1.1) in a first solvent, in the presence of KI and an antioxidant, reacting 4, 7-dichloroquinoline (formula I) with an amino side chain as shown in a formula II to obtain a reaction mixture containing hydroxychloroquine (formula III); and (1.2) separating the hydroxychloroquine from the reaction mixture containing the hydroxychloroquine; and (2) preparation of hydroxychloroquine sulfate: (2.1) in a second inert solvent, reacting the hydroxychloroquine obtained in the step (1) with sulfuric acid to form a salt so as to obtain the hydroxychloroquine sulfate (formula IV).

CRYSTALS OF HYDROXYCHLOROQUINE SULFATE

Two crystals of (S)-(+)-hydroxychloroquine sulfate. One crystal features diffraction peaks at 12.3±0.1°, 13.1±0.1°, 17.9±0.1°, 22.8±0.1°, 23.4±0.1°, 25.1±0.1°, and 26.3±0.1° as 2θ angles in a powder X-ray diffraction pattern. The other crystal features diffraction peaks at 12.8±0.1°, 14.5±0.1°, 16.7±0.1°, 17.6±0.1°, 20.2±0.1°, 21.4±0.1°, 23.8±0.1°, 25.7±0.1°, and 26.0±0.1° as 2θ angles in a powder X-ray diffraction pattern. Also disclosed are methods of preparing crystals of (S)-(+)-hydroxychloroquine sulfate.

TREATMENT OR PREVENTION OF CORONAVIRIDAE INFECTION

A method of treating or preventing a Coronaviridae infection in a subject comprising administrating a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt, ester or prodrug thereof to the subject in need thereof, wherein R1 is OH or H, and the Coronaviridae comprises at least one selected from 2019-nCov virus, HCov 229E virus, SARS virus, MERS virus.

Medicine for Covid-19 and treatment

The invention concerns a medicine and a prophylactic medicine for COVID-19 disease. The inventive medicine targets the endosomic, non-endosomic and/or intracellular viral pathways and inhibits them. The best mode of the invention is considered to be the medicine that blocks all three viral pathways. In the best mode the individual dose of a constituent component of the medicine is arranged to a dosage size sufficient to inhibit its designated SARS-CoV-2 viral pathway. This allows the dose of a particular pharmacological agent to be smaller than in a drug with just one kind of pharmacological agent. The best mode of the invention shuts the two cell membrane viral pathways and the one intracellular viral pathway with the minimum efficient dose, thereby preventing drug overdose, and enabling prophylactic or preventive use.

Preparation method of hydroxychloroquine sulfate

The invention relates to a preparation method of hydroxychloroquine sulfate, and belongs to the technical field of medicine synthesis. According to the preparation method of hydroxychloroquine sulfate, 7-chloro-4-fluoroquinoline and 5-(N-ethyl-N-2-hydroxyethyl amine)-2-pentylamine are subjected to a reaction to prepare hydroxychloroquine, and then hydroxychloroquine and sulfuric acid are salifiedto prepare hydroxychloroquine sulfate. The 7-chloro-4-fluoroquinoline is prepared from 4,7-dichloroquinoline through a halogen exchange reaction. The preparation method of hydroxychloroquine sulfate has the advantages of low reaction temperature, short reaction time, fewer byproducts, simple technique and favorable reproducibility, and is beneficial to industrial production.