63-45-6 Usage
Uses
Used in Antimalarial Applications:
Primaquine diphosphate is used as an antimalarial drug for its ability to eliminate late-stage gametocytes and hypnozoites, which are responsible for persistent liver forms of P. vivax or P. ovale infection.
Used in Acetylcholinesterase Inhibition:
Primaquine diphosphate is also used as an acetylcholinesterase inhibitor, which can help in the treatment of certain neurological disorders by increasing the levels of acetylcholine in the brain.
Used in Historical Research:
Primaquine diphosphate has played a significant role in the discovery of glucose-6-phosphate (G6P) dehydrogenase deficiency. Its use in treating malaria led to the identification of hemolytic anemia in patients lacking the G6P-metabolizing enzyme, contributing to a better understanding of this genetic condition.
Biological Activity
primaquine, an 8-aminoquinoline, is introduced as a curative antimalarial agent in 1950. since then, the drug has been applied extensively to against the exoerythrocytic stage of malaria. it is demonstrated tthat primaquine, by binding to nucleic acids, could therefore block protein synthesis, alter lipid synthesis and interact with biological membranes. [1]
Clinical Use
Treatment of malaria (Plasmodium vivax and
Plasmodium ovale), in combination with chloroquine
Treatment of Pneumocystis jiroveci pneumonia
(PCP), in combination with clindamycin
in vitro
chicken embryo cells (cec) model were adopted to investigate the effect of primaquine on newcastle disease virus replication. it was found that virus-induced hemadsorption was inhibited by primaquine in a dose-dependent manner and was completely suppressed by primaquine 250 g/ml. viral ribonucleic acid (rna) synthesis was found to be suppressed when primaquine was added early in the virus replication cycle. whereas, when the drug was added late in the cycle, rna synthesis was stimulation. [1]
in vivo
primaquine liposomes were labelled by 99mtc and injected intravenously to swiss albino mice. after injection, the major accumulation organ of liposomes was liver followed by spleen, pancreas, lungs and the others. findings also suggested that primaquine could block the eradication of the parasites and prevent relapse by destruction of the exoerythrocytic liver stages. [2]
Drug interactions
Potentially hazardous interactions with other drugs
Antimalarials: avoid concomitant use with
artemether/lumefantrine.
Metabolism
Rapidly metabolised in the liver. Its major metabolite
carboxyprimaquine accumulates in the plasma on
repeated dosage but possesses less antimalarial activity
than the parent compound.
Little unchanged drug is excreted in the urine.
Purification Methods
It forms yellow crystals from 90% aqueous EtOH and is moderately soluble in H2O. The oxalate salt has m 182.5-185o (from 80% aqueous EtOH), and the free base is a viscous liquid b 165-170o/0.002mm, 175-177o/2mm. [Elderfield et al. J Am Chem Soc 68 1526 1964, Elderfield et al. J Am Chem Soc 77 4817 1955, Beilstein 22 III/IV 5817.]
references
[1]burdick jr and durand dp. primaquine diphosphate: inhibition of newcastle disease virus replication. antimicrob agents ch. 1974 oct 15; 6(4): 460-4.[2]aricat b, ozert ay, ercans mt and hincalt aa. characterization, in vitro and in vivo studies on primaquine diphosphate liposomes. j. microencapsulation. 1995; 12(5): 469-85.[3]soto j, toledo j, rodriquez m, sanchez j, herrera r, padilla j and berman j. double-blind, randomized, placebo-controlled assessment of chloroquine/primaquine prophylaxis for malaria in nonimmune colombian soldiers. clin infect dis. 1999 jul; 29: 199-201.
Check Digit Verification of cas no
The CAS Registry Mumber 63-45-6 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 6 and 3 respectively; the second part has 2 digits, 4 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 63-45:
(4*6)+(3*3)+(2*4)+(1*5)=46
46 % 10 = 6
So 63-45-6 is a valid CAS Registry Number.
InChI:InChI=1/C15H21N3O.2H3O4P/c1-11(5-3-7-16)18-14-10-13(19-2)9-12-6-4-8-17-15(12)14;2*1-5(2,3)4/h4,6,8-11,18H,3,5,7,16H2,1-2H3;2*(H3,1,2,3,4)
63-45-6Relevant academic research and scientific papers
Preparation method of primaquine phosphate
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Paragraph 0055-0072, (2021/08/14)
The invention discloses a preparation method of primaquine phosphate, which is characterized by comprising the following steps of: adding a secondary condensate, ethanol and hydrazine hydrate into a reaction container, introducing nitrogen for protection, stirring in a dark place, heating to 78-80 DEG C, carrying out reflux reaction until the reaction is complete, evaporating ethanol under normal pressure until the internal temperature is increased to 92-95 DEG C, adding water, stirring, heating to 58-62 DEG C to enable no solid to suspend, cooling to 40-50 DEG C, dropwise adding a sodium hydroxide solution with the mass concentration of 25-30% while stirring to enable the pH to be 13-14, stirring, adding methylbenzene, stirring, standing for layering, adding water into an organic phase for washing, then decolorizing with activated carbon, filtering and concentrating to obtain free primaquine oil, and adding dichloroethane for crystallization to obtain free primaquine. By adjusting process parameters (such as reaction temperature, time, light shielding, nitrogen protection and charging sequence) of each step, a dichloroethane crystallization process of free primaquine is added, the purity of a finished product is greater than 99.5%, the content of a single impurity is less than 0.2%, and the yield is high.
Synthesis of primaquine glyco-conjugates as potential tissue schizontocidal antimalarial agents
Azad, Chandra S.,Saxena, Mridula,Siddiqui, Arif J.,Bhardwaj, Jyoti,Puri, Sunil K.,Dutta, Guru P.,Anand, Nitya,Saxena, Anil K.
, p. 254 - 261 (2017/07/13)
Primaquine (PQ) is the only drug used to prevent relapse of malaria due to P. vivax and P. ovale, by eradicating the dormant liver form of the parasite (hypnozoites). The side-effects associated with PQ limits is uses in treatment of malaria. To overcome the premature oxidative deamination and to increase the life span of drug in the biological system, the novel glyco-conjugates of PQ were synthesized by coupling of primaquine with hexoses in phosphate buffer. The saccharide part of the hybrid molecules thought to direct the drug to the liver, where hypnozoites resides. All the synthesized compounds were fully characterized and evaluated for their radical curative activities. The three compounds viz glucoside (15a), galactoside (15b) and mannoside (15c) with high activity were tested for their activity in rhesus monkeys where the most active compound 15b showed twofold activity (100% radical curative activity at 1.92?mmol/kg) than the standard drug PQ diphosphate (3.861?mmol/kg). It is proposed that results from these studies may be advantageous to develop a new potent tissue schizonticide antimalarial compound.
