Amodiaquine

Amodiaquine Basic information
Product Name:Amodiaquine
Synonyms:4-((7-chloro-4-quinolyl)amino)-alpha-(diethylamino)-o-creso;4-((7-Chloro-4-quinolyl)amino)-alpha-(diethylamino)-o-cresol;4-[(7-Chloro-4-quinolinyl)amino]-alpha-(diethylamino)-o-cresol;7-Chloro-4-(3-diethylaminomethyl-4-hydroxyphenylamino)quinoline;Amodiaquine, ring-closed;CAM-AQ1;CAM-AQI;Camochin
CAS:86-42-0
MF:C20H22ClN3O
MW:355.86
EINECS:201-669-3
Product Categories:Amines;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;Heterocycles
Mol File:86-42-0.mol
Amodiaquine Structure
Amodiaquine Chemical Properties
Melting point 208°C
Boiling point 478.0±45.0 °C(Predicted)
density 1.258
storage temp. -20°C Freezer
solubility DMSO (Slightly, Sonicated), Methanol (Slightly)
form Solid
pka9.43±0.50(Predicted)
color Pale Yellow to Light Yellow
CAS DataBase Reference86-42-0(CAS DataBase Reference)
NIST Chemistry ReferenceAmodiaquine(86-42-0)
Safety Information
Hazardous Substances Data86-42-0(Hazardous Substances Data)
ToxicityLD50 oral in mouse: 550mg/kg
MSDS Information
Amodiaquine Usage And Synthesis
DescriptionAmodiaquine is a prodrug form of the antimalarial compound N-desethyl amodiaquine . It is active against several strains of P. falciparum in vitro (EC50s = 0.23-0.52 nM) and exhibits a synergistic effect when used in combination with N-desethyl amodiaquine. Amodiaquine dose-dependently inhibits development of parasitemia in a mouse model of P. berghei infection.
Chemical PropertiesCyrstalline Solid
OriginatorCamoquin HCl,Parke Davis,US,1950
UsesAn antimalarial
DefinitionChEBI: A quinoline having a chloro group at the 7-position and an aryl amino group at the 4-position.
IndicationsAmodiaquine (Camoquin) is another 4-aminoquinoline derivative whose antimalarial spectrum and adverse reactions are similar to those of chloroquine, although chloroquine-resistant parasites may not be amodiaquine- resistant to the same degree. Prolonged treatment with amodiaquine may result in pigmentation of the palate, nail beds, and skin. There is a 1:2000 risk of agranulocytosis and hepatocellular dysfunction when the drug is used prophylactically.
Manufacturing Process72.8 g (0.5 mol) of p-aminophenol hydrochloride is dissolved in 500 cc of water and added to 99 g (0.5 mol) of 4,7-dichloroquinoline. After a few minutes of warming in a steam bath, 4-(4'-hydroxyanilino)-7-chloroquinoline hydrochloride, of sufficient purity for use in further experiments, precipitates as a yellow crystalline solid. Recrystallized from methanol, the MP is over 300°C.
A mixture consisting of 13.5 g of 4-(4'-hydroxyanilino)-7-chloroquinoline hydrochloride dissolved in absolute ethanol is treated with a solution of 4.38 g of diethylamine and 1.8 g of paraformaldehyde in 20 cc of absolute ethanol. The reaction mixture is heated under reflux for 16 hours, evaporated to onehalf volume and the warm solution treated with an excess of hydrogen chloride dissolved in absolute ethanol. Acetone is added to the warm solution until it becomes turbid and then the solution is cooled. The crude dihydrochloride which separates is collected and purified by recrystallization from methanol; MP 240-242°C.
By using an equivalent amount of 4-(4'-hydroxyanilino)-7-bromoquinoline in the above procedure, 4-(3'-diethylaminomethyl-4'-hydroxyanilino)-7- bromoquinoline dihydrochloride is obtained; MP (base) 206-208°C dec.

Brand nameCamoquin (Parke-Davis);Amodoquin tablets;Basoquin;Caniquin.
Therapeutic FunctionAntimalarial
World Health Organization (WHO)Amodiaquine, an antimalarial agent related to chloroquine, was introduced over 40 years ago for the treatment and prophylaxis of malaria. The drug was voluntarily withdrawn in the United Kingdom in 1975 for commercial reasons but was subsequently reintroduced in 1985 to meet the medical demand for an antimalarial drug to deal with the rapid spread of chloroquine-resistant falciparum malaria in Asia and Africa. By 1986 a significant number of cases of agranulocytosis associated with prophylactic use, some of which were fatal, had been reported there and it has been estimated that the frequency of this risk is of the order of 1:2,000. Although most cases occurred when amodiaquine had been used in combination with other antimalarials, the major manufacturer decided to withdraw the prophylactic indication worldwide following discussions with experts. Preparations remain available for the treatment of acute attacks of malaria which involves only a short period of exposure to the drug. (Reference: (WHODI) WHO Drug Information, 1, 5, 1987)
Pharmaceutical ApplicationsA mono-Mannich-base 4-aminoquinoline, formulated as the dihydrochloride dihydrate or free base for oral administration. It is active against P. falciparum and P. vivax and is more active than chloroquine for the treatment of uncomplicated P. falciparum malaria. Chloroquine-resistant strains may remain susceptible, but resistance to amodiaquine is also spreading in some regions of Africa. The pharmacological properties are similar to those of chloroquine. The terminal elimination halflife is 1–3 weeks. It is rapidly and extensively metabolized to the desethyl derivative which has reduced antiplasmodial activity. Prophylactic use has been abandoned because of agranulocytosis and hepatotoxicity due to formation of a quinoneimine metabolite. A fixed dose combination with artesunate and derivatives (for example, isoquine) with altered metabolism and reduced toxicity is in development.
Clinical UseTreatment of falciparum malaria
Clinical UseMechanistically, it is very similar to chloroquine and does nothave any advantages over the other 4-aminoquinoline drugs.When used for prophylaxis of malaria, it had a higher incidenceof hepatitis and agranulocytosis than that was chloroquine.There is evidence that the hydroquinone (phenol)amine system readily oxidizes to a quinone imine either autoxidatively and/or metabolically, and this productmay contribute to amodiaquine’s toxicity.
SynthesisAmodiaquin, 4-[(7-chloro-4-quinilyl)amino]-|á-diethylmaino-o-cresol (37.1.1.21), is made by reacting 4,7-dichloroquineoline (37.1.1.1) with 4-aminophenol to make 7-chloro-4-(4-hydroxyphenylamino)-quiniline (37.1.1.20), which then undergoes an aminomethylation reaction using formaldehyde and diethylamine, giving amodiaquin.

Synthesis_86-42-0

Purification MethodsAmodiaquin crystallises from 2-ethoxyethanol or EtOH. [Burckhalter et al. J Am Chem Soc 70 1363 1948, Beilstein 22 III/IV 4647.]
Amodiaquine Preparation Products And Raw materials
Raw materials4-Hydroxyaniline hydrochloride-->4,7-Dichloroquinoline-->Diethylamine-->Paraformaldehyde
Methylparaben Primaquine Primaquine diphosphate Methyl Chloroacetic acid Phenol Red Phenol Tribenuron methyl Difluorochloromethane 4-Aminophenol Methanol Amorolfine Hydrochloride AMODIAQUINE HYDROCHLORIDE,AMODIAQUINE DIHYDROCHLORIDE,AMODIAQUINE HCL Amodiaquine Epichlorohydrin Methyl salicylate Methyl acrylate Amorolfine

Email:[email protected] [email protected]
Copyright © 2024 Mywellwork.com All rights reserved.