Hydroxychloroquine sulfate cas：747-36-4 Basic information
|Product Name:||Hydroxychloroquine sulfate|
Hydroxychloroquine sulfate cas：747-36-4 Chemical Properties
White or practically white crystalline powder, Is odorless and has a bitter taste
A 、B、 C符合规定
Freely soluble in water,practically insoluble in alcohol,in chloroform,and in ether
Loss on drying
乙醇 Ethanol ≤5000ppm
乙酸乙酯 Ethyl acetate≤5000ppm
异丙醇 Isopropanol ≤5000ppm
Complies with USP41 standards.
|Chemical Properties||White Cyrstalline Solid|
|Uses||antimalarial, lupus suppressant|
|Uses||An antimalarial; antirheumatic; lupus erythematosus suppressant|
|Manufacturing Process||A mixture of 323 grams of 1-chloro-4-pentanone, 480 grams of N-ethyl-N-2- hydroxyethylamine and 400 grams of sodium chloride (to aid in subsequent filtration) in 1.3 liters of xylene was heated with stirring on a steam bath for two hours and then refluxed for three hours. After standing overnight, the mixture was filtered and the filter cake washed with xylene. The filtrate was fractionally distilled, yielding 207.3 grams of a fraction distilling at 89° to 90°C at 0.35 mm; nD25 = 1.4600. This fraction, 1-(N-ethyl-N-2- hydroxyethylamino)-4-pentanone, was used in the next step of the synthesis. A sample of the fraction was further purified by distillation through a column and gave an analytically pure sample of 1-(N-ethyl-N-2-hydroxyethylamino)- 4-pentanone, boiling at 85° to 87°C at 0.4 mm.|
The 1-(N-ethyl-N-2-hydroxyethylamino)-4-pentanone from above (284.2 grams) was dissolved in 300 grams of 28% ammoniacal methanol and reduced catalytically with Raney nickel (at an initial pressure of 1,000 pounds) at room temperature. After 24 hours the catalyst was filtered off and the product distilled in vacuo through a column, yielding 254 grams of a fraction distilling at 88.5° to 96°C at 0.3 mm and comprising mainly 5-(N-ethyl-N-2- hydroxyethylamino)-2-pentylamine. An analytical sample of this fraction distilled at 93°C at 0.6 mm.
A mixture of 90 grams of 4,7-dichloroquinoline, 90 grams of phenol, 1 gram of potassium iodide and 132 grams of 5-(N-ethyl-N-2-hydroxyethylamino)-2- pentylamine from above was heated with stirring for 13 hours at 125° to 130°C. Methanol (1.9 liters) was added and the the mixture was filtered with charcoal. The filtrate was treated with 270 cc of a solution of 100 grams of phosphoric acid in 300 cc of methanol. The walls of the flask containing the filtrate were scratched with a glass rod and the mixture was allowed to stand for two days. The solid was filtered off, washed with methanol and dried, yielding 101 grams of crude 7-chloro-4-[5-(N-ethyl-N-2-hydroxyethylamino)- 2-pentyl]aminoquinoline diphosphate, MP 155° to 156°C.
Additional quinoline diphosphate was obtained as a gummy mass from the filtrate by concentrating the latter to about half its volume and adding acetone. The crude gummy diphosphate was dissolved in water, basified with ammonium hydroxide and the resulting liberated basic quinoline extracted with chloroform. After removal of the chloroform by distillation, the residue was dissolved in ether and crystallization was induced by scratching the walls of the flask with the glass rod. About 30 grams of the crude quinoline base, melting at 77° to 82°C, separated. Recrystallization of this material from ethylene dichloride or ethyl acetate yielded the purified 7-chloro-4-[5-(Nethyl-N-2-hydroxyethylamino)2-pentyl] aminoquinoline, MP 89° to 91°C. The base may then be dissolved in ethanol and precipitated as the sulfate by reaction with an equimolar quantity of sulfuric acid.
|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.
|Hydroxychloroquine sulfate Preparation Products And Raw materials|
|Raw materials||Ammonia-->Sulfuric acid-->Hydrogen-->4,7-Dichloroquinoline-->2-(Ethylamino)ethanol-->Phosphoric acid-->5-Chloro-2-pentanone|