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Hydroxychloroquine is a synthetic antimalarial agent which can also inhibit Toll-like receptor 7/9 (TLR7/9) signaling.
Hydroxychloroquine is efficiently inhibits SARS-CoV-2 infection in vitro.
Hydroxychloroquine, an analogue of chloroquine, was developed in 1946.
CAS: 118-42-3
MF: C18H26ClN3O
MW: 335.88
EINECS: 2042498
Synonyms
2-((4-((7-chloro-4-quinolyl)amino)pentyl)ethylamino)-ethano;2-((4-((7-chloro-4-quinolyl)amino)pentyl)ethylamino)ethanol;7-chloro-4-(4-(n-ethyl-n-beta-hydroxyethylamino)-1-methylbutylamino)quinolin;7-chloro-4-(5-(n-ethyl-n-2-hydroxyethylamino)-2-pentyl)aminoquinoline;hydroxychloroquine;plaquenil;win1258;Ethanol, 2-[[4-[(7-chloro-4-quinolinyl)amino]pentyl]ethylamino]-
Hydroxychloroquine and chloroquine are FDA-approved to treat or prevent malaria.
Hydroxychloroquine is also FDA-approved to treat autoimmune conditions such as chronic discoid lupus erythematosus, systemic lupus erythematosus in adults, and rheumatoid arthritis.
Hydroxychloroquine is often taken in combination with other drugs such as methotrexate.
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.
Hydroxychloroquine, like chloroquine, is a 4-aminoquinoline derivative used for the suppressive and acute treatment of malaria.
Hydroxychloroquine 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 Hydroxychloroquine may exacerbate these conditions.
Hydroxychloroquine, sold under the brand name Plaquenil among others, is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquine.
Other uses include treatment of rheumatoid arthritis, lupus, and porphyria cutanea tarda.
Hydroxychloroquine is taken by mouth, often in the form of hydroxychloroquine sulfate.
Common side effects may include vomiting, headache, blurred vision, and muscle weakness.
Severe side effects may include allergic reactions, retinopathy, and irregular heart rate.
Although all risk cannot be excluded, it remains a treatment for rheumatic disease during pregnancy.
Hydroxychloroquine is in the antimalarial and 4-aminoquinoline families of medication.
Hydroxychloroquine was approved for medical use in the United States in 1955.
Hydroxychloroquine is on the World Health Organization's List of Essential Medicines.
In 2023, Hydroxychloroquine was the 131st most commonly prescribed medication in the United States, with more than 4 million prescriptions.
Hydroxychloroquine has been studied for an ability to prevent and treat coronavirus disease 2019 (COVID-19), but clinical trials found it ineffective for this purpose and a possible risk of dangerous side effects.
Among studies that deemed hydroxychloroquine intake to cause harmful side effects, a publication by The Lancet was retracted due to data flaws.
The speculative use of hydroxychloroquine for COVID-19 threatens its availability for people with established indications.
Hydroxychloroquine is a disease-modifying anti-rheumatic drug (DMARD).
Hydroxychloroquine 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 a medication that treats autoimmune conditions like rheumatoid arthritis and lupus.
Hydroxychloroquine slows down your overactive immune system.
Hydroxychloroquine can also prevent and treat malaria by killing the parasite that causes it.
Hydroxychloroquine is a synthetic compound primarily used as an antimalarial and immunomodulatory agent.
Hydroxychloroquine belongs to the class of drugs known as 4-aminoquinolines and is characterized by its ability to inhibit the growth of certain parasites, particularly Plasmodium species, which cause malaria.
The chemical structure of hydroxychloroquine includes a hydroxyl group, which enhances its solubility and bioavailability compared to its predecessor, chloroquine.
Hydroxychloroquine is also utilized in the treatment of autoimmune diseases such as rheumatoid arthritis and lupus erythematosus due to its immunosuppressive properties.
Hydroxychloroquine functions by interfering with the communication of immune cells and modulating inflammatory responses.
Hydroxychloroquine is generally well-tolerated, but it can have side effects, including gastrointestinal disturbances and potential retinal toxicity with long-term use.
Hydroxychloroquine's mechanism of action involves the alteration of lysosomal pH, which affects antigen processing and presentation.
Hydroxychloroquine has gained attention in recent years for its potential role in treating viral infections, although its efficacy in this context remains under investigation.
History
Chloroquine was discovered by Hans Andersag and coworkers at the Bayer laboratories in 1934.
Hydroxychloroquine is a a synthetic analogue with the same mechanism of action with quinine.
This was introduced into clinical practice in 1947 for the prophylactic treatment of malaria.
Researchers subsequently attempted to discover structural analogs with superior properties and one of these was hydroxychloroquine.
Hydroxychloroquine Chemical Properties
Melting point: 89-91°
Boiling point: 516.7±50.0 °C(Predicted)
density: 1.1438 (rough estimate)
refractive index: 1.5790 (estimate)
storage temp.: Keep in dark place,Sealed in dry,Room Temperature
solubility: Chloroform (Slightlly), DMSO (Slightly), Methanol (Slightly)
form: Solid
pka: 14.76±0.10(Predicted)
color: White to Off-White
BCS Class: 2
InChI: InChI=1S/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)
InChIKey: XXSMGPRMXLTPCZ-UHFFFAOYSA-N
NIST Chemistry Reference: Hydroxychloroquine(118-42-3)
EPA Substance Registry System: Hydroxychloroquine (118-42-3)
Uses
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).
Hydroxychloroquine 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.
Hydroxychloroquine may be as long as 12 weeks before you notice the benefits.
In Rheumatic Arthritis:
Hydroxychloroquine lacks the myelosuppressive, hepatic, and renal toxicities seen with some other DMARDs, which simplifies monitoring.
Hydroxychloroquine's onset may be delayed for up to 6 weeks, but the drug should not be considered a therapeutic failure until after 6 months of therapy with no response.
Short-term toxicities include GI (nausea, vomiting, diarrhea), ocular (accommodation defects, benign corneal deposits, blurred vision, scotomas, night blindness, preretinopathy), dermatologic (rash, alopecia, skin pigmentation), and neurologic (headache, vertigo, insomnia) effects.
Periodic ophthalmologic examinations are necessary for early detection of reversible retinal toxicity.
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.
Hydroxychloroquine treats rheumatic disorders such as systemic lupus erythematosus, rheumatoid arthritis, and porphyria cutanea tarda, and certain infections such as Q fever and certain types of malaria.
Hydroxychloroquine is considered the first-line treatment for systemic lupus erythematosus.
Certain types of malaria, resistant strains, and complicated cases require different or additional medication.
Hydroxychloroquine blocks the effects of some chemicals released in autoimmune diseases, and is used to treat inflammatory conditions.
Hydroxychloroquine is widely used to treat primary Sjögren syndrome but does not appear to be effective.
Hydroxychloroquine is widely used in the treatment of post-Lyme arthritis.
Hydroxychloroquine may have both an anti-spirochete activity and an anti-inflammatory activity, similar to the treatment of rheumatoid arthritis.
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.
