86-42-0 Usage
Description
Amodiaquine 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 Properties
Cyrstalline Solid
Uses
An antimalarial
Definition
ChEBI: A quinoline having a chloro group at the 7-position and an aryl amino group at the 4-position.
Indications
Amodiaquine (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.
Brand name
Camoquin (Parke-Davis);Amodoquin tablets;Basoquin;Caniquin.
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drug was voluntarily withdrawn in the United Kingdom in 1975 for commercial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 Applications
A 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 Use
Different sources of media describe the Clinical Use of 86-42-0 differently. You can refer to the following data:
1. Treatment of falciparum malaria
2. Mechanistically, 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.
Synthesis
Amodiaquin, 4-[(7-chloro-4-quinilyl)amino]-α-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.
Purification Methods
Amodiaquin crystallises from 2-ethoxyethanol or EtOH. [Burckhalter et al. J Am Chem Soc 70 1363 1948, Beilstein 22 III/IV 4647.]
Check Digit Verification of cas no
The CAS Registry Mumber 86-42-0 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 8 and 6 respectively; the second part has 2 digits, 4 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 86-42:
(4*8)+(3*6)+(2*4)+(1*2)=60
60 % 10 = 0
So 86-42-0 is a valid CAS Registry Number.
InChI:InChI=1/C20H22ClN3O/c1-3-24(4-2)13-14-11-16(6-8-20(14)25)23-18-9-10-22-19-12-15(21)5-7-17(18)19/h5-12,25H,3-4,13H2,1-2H3,(H,22,23)
86-42-0Relevant articles and documents
GREEN CHEMISTRY SYNTHESIS OF THE MALARIA DRUG AMODIAQUINE AND ANALOGS THEREOF
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Paragraph 0073; 0074, (2013/09/26)
Methods are provided for a green chemistry one-pot synthesis of amodiaquine and amodiaquine analogs. The methods have a lower environmental impact, lower investment cost, reduced amounts of byproducts and impurities, and a shorter synthesis time, compared to current conventional synthesis methods. The methods reduce the total number of steps in the synthesis from four to five down to two, thereby simplifying production; and allow a reduced number of solvents and reagents to be used in production, thereby reducing the waste generated in the synthesis. The methods can reduce the waste to about 3-5 kilograms of waste generated per kilogram of product produced; and surprisingly improve the overall yield from 60-65% to greater than 90% as compared to the current conventional synthesis methods for amodiaquine and its analogs.
High molecular weight prodrug derivatives of antiinflammatory drugs
-
, (2008/06/13)
Compounds of the formula 1, PS - O - A - (CH2)n- B - D (1), wherein PS-O represents an alkoxide residue of any of the free hydroxy groups of a polysaccharide (PS-OH) compound with molecular weight (Mw) of from 40,000 to 5,000,000 selected from dextran, carboxymethyl dextran, diethylaminoethyl dextran, starch, hydroxyet-hyl starch, alginates, glycogen, pullullan, agarose, cellulose, chitosan, chitin and carrageenan,A is a carbonyl group or absent,n is zero or a positive integer from 1 to 14,B is oxygen, a carbonyl group, NR wherein R is hydrogen or lower alkyl, or B is absent, and, D is (i) a group of the formula:, R1 - CO - (11), wherein R1-CO- represents the acyl residue of a carboxylic acid drug (R1-COOH) used in the treatment of inflammatory disorders; or (ii) a group of the formula:, R2 - O - (12), wherein R2-O- refers to the C-21 alkoxide residue of a known antiinflammatory steroid (R2-OH) or an alkoxide residue of any other drug or medicament containing a hydroxy functional group used in the treatment of inflammatory disorders; with the proviso that when A is absent, n is 0, and B is absent, then R1-CO- is different from the acyl residue of acetylsalicylic acid;, and non-toxic pharmaceutically acceptable acid addition salts thereof;, and non-toxic pharmaceutically acceptable cation salts thereof. Such compounds are biolabile prodrugs providing controlled release and prolonged duration of action of the parent active antiinflamma-tory agents locally at the administration site after intra-articular, intra-muscular, subcutaneous or extra-dural application while at the same time being highly stable in aqueous solution in the pH range 3--5. After oral administration of such prodrugs the parent drug is liberated selectively in the terminal ileum and the colon over an extended period of time.
