Chloroquine

Base Information

• Chemical Name: Chloroquine
• CAS No.: 54-05-7
• Deprecated CAS: 56598-66-4
• Molecular Formula: C18H26 Cl N3
• Molecular Weight: 319.878
• Hs Code.: 2933499090
• European Community (EC) Number: 200-191-2
• NSC Number: 187208
• UNII: 886U3H6UFF
• DSSTox Substance ID: DTXSID2040446
• Nikkaji Number: J107.997B
• Wikipedia: Chloroquine
• Wikidata: Q422438
• NCI Thesaurus Code: C61671
• RXCUI: 2393
• Pharos Ligand ID: 4P9RDYHQL13F
• Metabolomics Workbench ID: 143482
• ChEMBL ID: CHEMBL76
• Mol file: 54-05-7.mol

Synonyms:Aralen;Arechine;Arequin;Chingamin;Chlorochin;Chloroquine;Chloroquine Sulfate;Chloroquine Sulphate;Khingamin;Nivaquine;Sulfate, Chloroquine;Sulphate, Chloroquine

Chemical Property of Chloroquine

Chemical Property:

• Appearance/Colour: White powder
• Vapor Pressure: 1.15E-08mmHg at 25°C
• Melting Point: 87 C
• Refractive Index: 1.592
• Boiling Point: 460.6 °C at 760 mmHg
• PKA: pKa 8.4(H2O t = 20) (Uncertain)
• Flash Point: 232.3 °C
• PSA: 28.16000
• Density: 1.111 g/cm^3/sup>
• LogP: 4.88360
• Storage Temp.: 2-8°C(protect from light)
• Solubility.: Chloroform (Slightly), Methanol (Slightly)
• XLogP3: 4.6
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 8
• Exact Mass: 319.1815255
• Heavy Atom Count: 22
• Complexity: 309

Purity/Quality:

98%,99%, ^*data from raw suppliers

Chloroquine ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antimalarial Agents
• Canonical SMILES: CCN(CC)CCCC(C)NC1=C2C=CC(=CC2=NC=C1)Cl
• Recent ClinicalTrials: Southeast Asia Dose Optimization of Tafenoquine
• Recent EU Clinical Trials: COVID-19: addition of azithromycin to chloroquine treatment
• Indications: Despite the presence of resistant P. falciparum parasites, chloroquine is still with few exceptions, the drug of choice for treatment of non-severe malaria in the semi-immune indigenous population in Africa south of the Sahara. It should, however, not be used in severe or complicated malaria. In areas with considerable risk for chloroquine resistant P. falciparum, the drug has to be combined with another antimalarial drug, e.g. proguanil, for effective prophylaxis. Chloroquine still remains the drug of choice for treatment and prophylaxis of malaria caused by the other forms of plasmodia except in New Guinea. Chloroquine is also useful for the treatment of amoebic hepatitis and in rheumatoid arthritis. Chloroquine (Aralen) is one of several 4-aminoquinoline derivatives that display antimalarial activity. Chloroquine is particularly effective against intraerythrocytic forms because it is concentrated within the parasitized erythrocyte. This preferential drug accumulation appears to occur as a result of specific uptake mechanisms in the parasite. Chloroquine appears to work by intercalation with DNA, inhibition of heme polymerase or by interaction with Ca++–calmodulinmediated mechanisms. It also accumulates in the parasite’s food vacuoles, where it inhibits peptide formation and phospholipases, leading to parasite death. Chloroquine may be the drug of choice, but only in areas where chloroquine-sensitive P. falciparum organisms are present. Chloroquine prophylaxis is no longer effective for travel to many regions. Daily atovaquone–proguanil appears to be the first choice for chemoprophylaxis for travel to areas of chloroquine resistance. Prophylactic drugs, such as chloroquine or mefloquine, should be started 2 to 4 weeks prior to travel and continued for 6 to 8 weeks after leaving the endemic areas. The atovaquone–proguanil combination is the exception in that it is started 1 to 2 days prior to departure and is continued 1 week after return.
• Description: Chloroquine is the most effective of the hundreds of 4-aminoquinolines synthesized and tested during World War II as potential antimalarials. Structure–activity relationships demonstrated that the chloro at the 8-position increased activity, whereas alkylation at C-3 and C-8 diminished activity. The replacement of one of its N-ethyl groups with an hydroxyethyl produced hydroxychloroquine, a compound with reduced toxicity that is rarely used today except in cases of rheumatoid arthritis.
• Uses: Medicine (antimalarial). Usually dispensed as the phosphate. CQ and HCQ are both used as anti-inflammatory and antimalarial drugs. Chloroquine used in the treatment of malaria and MDR-strains. It is a COVID19-related research product.
• Clinical Use: The drug is effective against all four types of malaria with the exception of chloroquine-resistant P. falciparum. Chloroquine destroys the blood stages of the infection and therefore ameliorates the clinical symptoms seen in P. malariae, P. vivax, P. ovale, and sensitive P. falciparum forms of malaria. The disease will return in P. vivax and P. ovale malaria, however, unless the liver stages are sequentially treated with primaquine after the administration of chloroquine. Chloroquine also can be used prophylactically in areas where resistance does not exist. In addition to its use as an antimalarial, chloroquine has been used in the treatment of rheumatoid arthritis and lupus erythematosus, extraintestinal amebiasis, and photoallergic reactions. Prophylaxis and treatment of all types of malaria Hepatic amebiasis (in sequential combination with dehydroemetine) A combination with azithromycin has been suggested for intermittent preventive treatment.
• Drug interactions: Potentially hazardous interactions with other drugs Anti-arrhythmics: increased risk of ventricular arrhythmias with amiodarone - avoid. Antibacterials: increased risk of ventricular arrhythmias with moxifloxacin - avoid; concentration of praziquantel reduced - consider increasing praziquantel dose. Anti-depressants: possible increased risk of ventricular arrhythmias with citalopram and escitalopram. Antiepileptics: antagonism of anticonvulsant effect. Antimalarials: increased risk of convulsions with mefloquine; avoid with artemether/lumefantrine. Antipsychotics: increased risk of ventricular arrhythmias with droperidol - avoid. Ciclosporin: increases ciclosporin concentration - increased risk of toxicity. Cytotoxics: possible increased risk of ventricular arrhythmias with bosutinib, ceritinib and panobinostat. Digoxin: possibly increased concentration of digoxin. Lanthanum: absorption possibly reduced by lanthanum, give at least 2 hours apart.

Technology Process of Chloroquine

There total 27 articles about Chloroquine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 94.0%

chloroquine phosphate (50-63-5,69698-56-2) → Chloroquine (54-05-7)

Guidance literature:

With sodium hydroxide; In water; ethyl acetate; at 0 ℃; for 1h;

Reference yield: 90.72%

4,7-dichloroquinoline (86-98-6,1138471-54-1) + 5-diethylamino-2-pentylamine (140-80-7) → Chloroquine (54-05-7)

Guidance literature:

With diethylamine; phenol; at 90 - 100 ℃; under 1140.08 Torr; Temperature; Reagent/catalyst; Pressure;

Reference yield: 82.5%

4,7-dichloroquinoline (86-98-6,1138471-54-1) + (R)-(-)-4-amino-1-(diethylamino)pentane (67459-50-1) → (R)-(-)-chloroquine (54-05-7,56598-66-4,58175-86-3,58175-87-4)

Guidance literature:

With potassium phosphate; palladium diacetate; bis[2-(diphenylphosphino)phenyl] ether; In toluene; at 80 - 85 ℃; for 2h; Solvent; Reagent/catalyst; Temperature; Inert atmosphere;

upstream raw materials:

uroporphyrin I - chloroquine complex

4,7-dichloroquinoline

5-diethylamino-2-pentylamine

7-chloro-4-bromo-quinoline

Downstream raw materials:

(R)-chloroquine phosphate

(R)-(-)-chloroquine

(S)-(+)-chloroquine phosphate

(R)-chloroquine phosphate

Refernces

• 1、 Kuter, David,Benjamin, Stefan J.,Egan, Timothy J.. "Multiple spectroscopic and magnetic techniques show that chloroquine induces formation of the μ-oxo dimer of ferriprotoporphyrin IX". . p. 40 - 49. Retrieved 2014.
• 2、 Fan, Jun,Guo, Dong,He, Rujian,Liang, Ziqing,Su, Wenxia,Zhang, Weiguang. "Enantioselective analyses of chloroquine and hydroxychloroquine in rat liver microsomes through chiral liquid chromatography–tandem mass spectrometry". supporting information. p. 126 - 133. Retrieved 2021/11/09.
• 3、 -. "Preparation method of chloroquine phosphate". Paragraph 0030-0036; 0039-0045; 0048-0054. . Retrieved 2021/05/26.