Hydroxychloroquine

Bezeichnung:Hydroxychloroquine

CAS-Nr118-42-3

Englisch Name:Hydroxychloroquine

CBNumberCB6866802

SummenformelC18H26ClN3O

Molgewicht335.88

MOL-Datei118-42-3.mol

Hydroxychloroquine physikalisch-chemischer Eigenschaften

Schmelzpunkt	89-91°
Siedepunkt	516.7±50.0 °C(Predicted)
Dichte	1.1438 (rough estimate)
Brechungsindex	1.5790 (estimate)
storage temp.	Keep in dark place,Sealed in dry,Room Temperature
Löslichkeit	Chloroform (Slightlly), DMSO (Slightly), Methanol (Slightly)
Aggregatzustand	Solid
pka	14.76±0.10(Predicted)
Farbe	White to Off-White
BCS Class	2
NIST chemische Informationen	Hydroxychloroquine(118-42-3)
EPA chemische Informationen	Ethanol, 2-[[4-[(7-chloro-4-quinolinyl)amino]pentyl]ethylamino]- (118-42-3)

Sicherheit

Toxizität

child,LDLo,oral,600mg/kg (600mg/kg),BRAIN AND COVERINGS: INCREASED INTRACRANIAL PRESSUREBEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLDCARDIAC: OTHER CHANGES,Journal of Analytical Toxicology. Vol. 14, Pg. 186, 1990.

Gefahreninformationscode (GHS)

Hydroxychloroquine Chemische Eigenschaften,Einsatz,Produktion Methoden

Originator
Plaquenil,Winthrop,US,1956
Verwenden
Hydroxychloroquine is used to treat autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, in addition to malaria.
Hydroxychloroquine is a disease-modifying anti-rheumatic drug (DMARD). It regulates the activity of the immune system, which may be overactive in some conditions. Hydroxychloroquine can modify the underlying disease process, rather than simply treating the symptoms.
Hydroxychloroquine is used to treat:
rheumatoid arthritis
discoid and systemic lupus erythematosus (SLE)
juvenile idiopathic arthritis (JIA).
Over the long term hydroxychloroquine can reduce pain, swelling and joint stiffness. If you have lupus, it may also improve the rash. It may be as long as 12 weeks before you notice the benefits.
Definition
ChEBI: An aminoquinoline that is chloroquine in which one of the N-ethyl groups is hydroxylated at position 2. An antimalarial with properties similar to chloroquine that acts against erythrocytic forms of malarial parasites, it is mainly used s the sulfate salt for the treatment of lupus erythematosus, rheumatoid arthritis, and light-sensitive skin eruptions.
Indications
Hydroxychloroquine (Plaquenil), like chloroquine, is a 4-aminoquinoline derivative used for the suppressive and acute treatment of malaria. It also has been used for rheumatoid arthritis and discoid and systemic lupus erythematosus. Hydroxychloroquine has not been proved to be more effective than chloroquine. Adverse reactions associated with its use are similar to those described for chloroquine.The drug should not be used in patients with psoriasis or porphyria, since it may exacerbate these conditions.
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.
Therapeutic Function
Antimalarial
Mechanism of action
Hydroxychloroquine, like chloroquine, is also used for treating acute forms of malaria caused by P. vivax, P. malariae, P. ovale, and also sensitive forms of P. falciparum. It is also effective and safe like chloroquine, although it does not have obvious advantages. The only advantage is that it is somewhat better tolerated. Its use is somewhat more limited than chloroquine. Synonyms of this drug are plaquenil, quensyl, toremonil, and others.
Clinical Use
Hydroxychloroquine is approved for the treatment of both systemic and cutaneous lupus erythematosus. Both chloroquine and quinacrine (Atabrine) are also effective in this skin disease. Low-dose chloroquine is used for the therapy of porphyria cutanea tarda in patients in whom phlebotomy has failed or is contraindicated. Other skin diseases in which the drugs are useful (after sunscreens and avoidance of sun exposure) include polymorphous light eruption and solar urticaria.
Synthese
Hydroxychloroquine, 7-chloro-4-[4-[ethyl(2-hydroxyethyl)amino]- 1-methylbutylamino]quinoline (37.1.1.19), is made by a scheme similar to that of making chloroquine. Reacting 1-chloro-4-pentanone with 2-ethylaminoethanol gives the corresponding aminoketone (37.1.1.17), which undergoes reductive amination in conditions analogous to those described above, making 4-[ethyl(2-hydroxyethyl)amino]-1-methylbutylamine (37.1.1.18). Reacting this with 4,7-dichlroquinoline (37.1.1.1) makes the desired hydroxychloroquine.

Hydroxychloroquine Upstream-Materialien And Downstream Produkte

Hydroxychloroquine Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

118-42-3 , Hydroxychloroquine Verwandte Suche:

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