Amodiaquin

There is heated under reflux with stirring for 10 hours 117 g of (2-phenyl-2-isoamyloxy )-ethyl bromide, 61 g of pyrrolidine and 250 ml of toluene. 

After filtration of the pyrrolidine hydrobromide, the toluene is removed under reduced pressure. The residue is then taken up with 4N HCI. The aqueous solution is washed with ether. It is made alkaline by a solution of 50% NaOH. It is extracted with ether. The ethereal phase is dried over anhydrous sodium sulfate, and rectified under reduced pressure after removing the solvent. There is thus obtained 90 g of a colorless oil with an amine odor. 

The hydrochloride is prepared in the usual manner by dissolving the amine in anhydrous ether and adding to it the requisite amount of dry gaseous hydrochloric acid,dissolved in absolute alcohol. There is obtained a white crystalline powder melting at 150°C, very soluble in water and alcohol,very slightly soluble in ether and ethyl acetate. 

The starting material above is prepared by reacting styrene with isoamyl alcohol and then reacting that product with t-butyl hypobromite. 

Centre Europeen de Recherches Mauvernay, R lOM British Patent 1,253,818 November 17, 1971 

Centre European de RecherchesMauvernay, RIOM British Patent 1,253618 November 17, 1971 

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Ammonium ion, JV-(2-thenyl)-N-benzyldimethyl-Stevens and Sommelet rearrangement, 4, 800 Ammonium salts, diallyldialkyl-polymerization, 1, 293 Ammonium salts, 2-pyrrolylmethyl-nucleophilic substitution abnormal, 4, 244 Sommelet rearrangement, 4, 244 Ammonium salts, trimethyl(l,3,5-triazinyl)-applications, 3, 525 Amobarbital, 3, 150 Amodiaquine, 1, 145 Amolanone applications, 4, 708... 

Amodiaquin [4-(3-dimethylaminomethyl-4-hydroxyanilino)-7-chloroquinoline] [86-42-0] M 287.5, m 208 . Crystd from 2-ethoxyethanol. 

Diethylacetylamino malonate Hydroxytryptophan Diet hy lal ly I-(1 -met hylbutyl) malonate Thiamylal Diethylamine Amodiaquin Benzquinamide Bialamicol Diethylpropion HCI Disulfiram Ethamivan... 

Amodiaquine, a Mannich base 4-aminoquinoline, eliminates blood stage parasites. Its mode of action is similar to that of chloroquine (see below) and there is some cross-resistance. 

Artemisinin and its derivatives, artesunate and arthemether, kill both asexual and sexual blood stages (Fig. 2). However, artemisinins are quickly eliminated from the body, resulting in parasite recrudescence, and are therefore combined with schizontocides that have a longer biological half-life, such as amodiaquine,... 

ACTs with amodiaquine, atovaquone-proguanil, chloroquine, clindamycin, doxycycline, lumefantrine,... 

ACTs are currently recommended artemether-lume-fantrine, artesunate + amodiaquine, artesunate + mefloquine, artesunate + sulfadoxine-pyrimethamine [1, 5]. In areas with amodiaquine and sulfadoxine-pyrimethamine resistance exceeding 20%, i.e., SE Asia, artesunate + mefloquine or artemether-lumefantrine should be used [1,5]. 

Y = primaquine, mepacrine, amodiaquine, lepidine, plasmoquine, pentaquine, and isopentaquine, have been reported.420 Similar studies of 27 complexes of general formula [IrY3], where... 

Abou-Ouf et al. [16] described a spectrophotometric method for the determination of primaquine phosphate in pharmaceutical preparation. Two color reactions for the analysis of primaquine phosphate dosage form, which are based on 2,6-dichlor-oquinone chlorimide and l,2-naphthoquinone-4-sulfonate, were described. The reactions depend on the presence of active centers in the primaquine molecule. These are the hydrogen atoms at position 5 of the quinoline nucleus and the primary amino group of the side chain. The method was applied to tablets of primaquine phosphate and a combination of primaquine phosphate and amodiaquine hydrochloride. 

Hassan et al [18] used a spectrophotometric method for the simultaneous determination of primaquine with amodiaquine mixtures in dosage forms. Crushed tablets containing primaquine phosphate and amodiaquine hydrochloride were extracted with 0.1 M hydrochloric acid, and the mixture was filtered. A portion of the filtrate was diluted with 0.1 M hydrochloric acid, and the absorbance of this solution was measured at 282 and 342 nm against hydrochloric acid. 

Chatterjee et al. [20] quantitatively separated primaquine from amodiquine by a selective precipitation method. A powdered sample containing primaquine and amodiaquine was dissolved in 0.01 N hydrochloric acid 4 N ammonia was added to precipitate amodiaquine. The mixture was filtered and the combined filtrate and washings containing primaquine was diluted with water and 0.1 N hydrochloric acid. The absorbance of this solution was measured at 282 nm versus a solvent blank. 

El-Ashry et al. [36] studied the complex formation between the bromophenol blue, primaquine, and other important aminoquinoline antimalarials. The colorimetric method used was described as simple and rapid and is based on the interaction of the drug base with bromophenol blue to give a stable ion-pair complex. The spectra of the complex show maxima at 415 420 nm with high apparent molar absorptivities. Beer s law was obeyed in the concentration range 1-8,2-10, and 2-12 pg/mL for amodiaquine hydrochloride, primaquine phosphate, and chloroquine phosphate, respectively. The method was applied to the determination of these drugs in certain formulations and the results were favorably comparable to the official methods. 

El-Kommos and Emara [47] determined primaquine and other secondary aromatic amines pharmaceuticals by a spectrophotometric method using 4-dimethyl amino cinnamaldehyde. The reaction of the reagent with primaquine and with the other amines was investigated. Powdered tablets were extracted with methanolic 0.1 M perchloric acid. The extract was mixed 1 1 with methanolic 0.2% of 4-dimethyl amino cinnamaldehyde and the mixture was diluted with methanol before measurement of the absorbance at 670 nm for primaquine phosphate. Beer s law was obeyed for 2-20 pg/mL of primaquine. The pink and green color formed with primaquine was stable for at least 24 h. Recoveries were good. Amodiaquine did not interfere with the determination of primaquine. 

Mohamed [63] investigated the complexation behavior of amodiaquine and primaquine with Cu(II) by a polarographic method. The reduction process at dropping mercury electrode in aqueous medium is reversible and diffusion controlled, giving well-defined peaks. The cathodic shift in the peak potential (Ep) with increasing ligand concentrations and the trend of the plot of EVl versus log Cx indicate complex formation, probably more than one complex species. The composition and stability constants of the simple complexes formed were determined. The logarithmic stability constants are log Bi = 3.56 log B2 = 3.38, and log B3 = 3.32 [Cu(II)-primaquine at 25 °C]. 

Maggs JL, Kitteringham NR, Breckenridge AM, et al. Autoxidative formation of a chemically reactive intermediate from amodiaquine, a myelotoxin and hepatotoxin in man. Biochem Pharmacol 1987 36(13) 2061-2062. 

H, X.Q., Bjorkman, A., Andersson, T.B., Ridderstrom, M. and Masimirembwa, C.M. (2002) Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2 C8 a new high affinity and turnover enzyme-specific probe substrate. Journal of Pharmacology and Experimental Therapeutics, 300 (2), 399-407. 

Materials Required Amodiaquine hydrochloride 0.3 g dilute ammonia solution (42.5 ml of strong ammonia solution to 100 ml in water) NO. 4 sintered glass crucible. 

Theory Amodiaquine hydrochloride possesses two moles of inherent water of crystallization, and hence the precentage base is calculated with reference to the substance dried over P205 at a pressure not exceeding 5 mm of Hg. Usually, the assay is performed on one portion of the sample and the drying on a separate portion altogether. 

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