747-36-4

Basic information

• Product Name: Hydroxychloroquine sulfate
• Synonyms: 2-((4-((7-chloro-4-quinolinyl)amino)pentyl)ethylamino)ethanolsulfate(1:1)(;7-Chloro-4-[4-(N-ethyl-N-b-hydroxyethylamino)-1-methylbutylamino]quinoline sulfate;2-((4-((7-Chloro-4-quinolinyl)amino)pentyl)ethylamino)ethanol sulfate (1:1) (salt);Ethanol, 2-((4-((7-chloro-4-quinolinyl)amino)pentyl)ethylamino)-, sulfate (1:1) (salt);Ethanol, 2-((4-((7-chloro-4-quinolyl)amino)pentyl)ethylamino)-, sulfate (1:1) (salt);Plaquinol;Hydroxychloroquine sulfate,98%;Hydroxychloroquin
• CAS NO: 747-36-4
• Molecular Formula: C18H28ClN3O5S
• Molecular Weight: 433.95
• EINECS: 212-019-3
• Product Categories: PLAQUENIL;API;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 747-36-4.mol
• Article Data: 23

Chemical Properties

• Melting Point: 240 °C
• Boiling Point: 516.7 °C at 760 mmHg
• Flash Point: 266.3 °C
• Appearance: white to off-white/Crystalline Powder
• Vapor Pressure: 1.68E-11mmHg at 25°C
• Storage Temp.: Refrigerator
• Solubility: H2O: >20mg/mL
• Water Solubility: FREELY SOLUBLE
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in water may be stored at -20°C for up to 3 months.
• Merck: 14,4818
• CAS DataBase Reference: Hydroxychloroquine sulfate(CAS DataBase Reference)
• NIST Chemistry Reference: Hydroxychloroquine sulfate(747-36-4)
• EPA Substance Registry System: Hydroxychloroquine sulfate(747-36-4)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 42/43-36/37/38-36-22
• Safety Statements: 37/39-26
• WGK Germany: 3
• RTECS: KK3342500
• Hazardous Substances Data: 747-36-4(Hazardous Substances Data)

Usage

Description

Different sources of media describe the Description of 747-36-4 differently. You can refer to the following data:
1. Hydroxychloroquine sulfate (also known as hydroxychloroquine) is an antimalarial medicine approved in the United States for either prevention or treatment of certain types of malaria, lupus erythematosus, and rheumatoid arthritis. It is sold under the brand name Plaquenil and it is also sold as a generic medicine. It is available in tablets of 155mg base (200mg salt). Hydroxychloroquine sulfate has not been approved for the treatment of COVID-19. It has been used experimentally to treat certain people with COVID-19, including hospitalized patients. Hydroxychloroquine sulfate is being used to try and stop the COVID-19 virus from spreading inside your body. This may help you to get better. Hydroxychloroquine sulfate is experimental because we do not know if it works for COVID-19. It is not approved by FDA for the treatment of COVID-19, but emergency use has been authorized for adults and adolescents who weigh 50 kg (110 pounds) or more and are hospitalized with COVID-19 if a clinical trial is not available or you are not able to participate in a clinical trial. There is limited information known about the safety and effectiveness (whether this will make you better) of using hydroxychloroquine sulfate for hospitalized patients with COVID-19.
2. Hydroxychloroquine is an aminoquinoline with antimalarial, anti-inflammatory, and antiviral activities. It is active against the chloroquine-sensitive NF54 and D6 strains of P. falciparum (IC50s = 16.3 and 15 nM, respectively) but has decreased activity against chloroquine-resistant P. falciparum strains (IC50s = 422.7-1,735.3 nM). Hydroxychloroquine inhibits production of IL-22, IL-17A, and IL-6 induced by phorbol 12-myristate 13-acetate (TPA; ) and ionomycin in peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals or patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). It inhibits accumulation of sequestosome-1 (SQSTM1) puncta, a marker of autophagy, in mouse embryonic fibroblasts (MEFs) in a concentration-dependent manner. Hydroxychloroquine reduces viral titers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the culture supernatant of infected Vero E6 cells but does not reduce SARS-CoV-2 viral titers in an in vitro human airway epithelium model or the respiratory tract of infected cynomolgus macaques. Formulations containing hydroxychloroquine have been used in the prevention or treatment of malaria, as well as in the treatment of RA and SLE.

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

Relevant articles and documents

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

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.

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.