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Details

Stereochemistry ACHIRAL
Molecular Formula C29H32Cl2N6.H3O4P
Molecular Weight 633.506
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PIPERAQUINE PHOSPHATE (1:1)

SMILES

OP(O)(O)=O.ClC1=CC=C2C(=C1)N=CC=C2N3CCN(CCCN4CCN(CC4)C5=C6C=CC(Cl)=CC6=NC=C5)CC3

InChI

InChIKey=KATNPMSTHHZOTK-UHFFFAOYSA-N
InChI=1S/C29H32Cl2N6.H3O4P/c30-22-2-4-24-26(20-22)32-8-6-28(24)36-16-12-34(13-17-36)10-1-11-35-14-18-37(19-15-35)29-7-9-33-27-21-23(31)3-5-25(27)29;1-5(2,3)4/h2-9,20-21H,1,10-19H2;(H3,1,2,3,4)

HIDE SMILES / InChI

Description
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20937779 | https://clinicaltrials.gov/ct2/show/NCT02788864 | https://www.ncbi.nlm.nih.gov/pubmed/18180357 | https://clinicaltrials.gov/ct2/show/NCT02590627

Piperaquine is a bisquinoline antimalarial drug that was first synthesized in the 1960s and used extensively in China and Indochina as prophylaxis and treatment during the next 20 years. Usage declined in the 1980s as piperaquine-resistant strains of P. falciparum arose and artemisinin-based antimalarials became available. However, during the next decade, piperaquine was rediscovered by Chinese scientists as one of a number of compounds suitable for combination with an artemisinin derivative. The rationale for such artemisinin combination therapies (ACTs) was to provide an inexpensive, short-course treatment regimen with a high cure rate and good tolerability that would reduce transmission and protect against the development of parasite resistance. Piperaquine is characterized by slow absorption and a long biological half-life, making it a good partner drug with artemisinin derivatives which are fast acting but have a short biological half-life.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
29.0 nM [IC50]
29.1 nM [IC50]
48.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Some considerations in the design and interpretation of antimalarial drug trials in uncomplicated falciparum malaria.
2006 Dec 22
Dihydroartemisinin-piperaquine versus artesunate-amodiaquine: superior efficacy and posttreatment prophylaxis against multidrug-resistant Plasmodium falciparum and Plasmodium vivax malaria.
2007 Apr 15
Randomized comparison of amodiaquine plus sulfadoxine-pyrimethamine, artemether-lumefantrine, and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso.
2007 Dec 1
Intermittent preventive treatment for the prevention of malaria during pregnancy in high transmission areas.
2007 Dec 4
A randomized open study to assess the efficacy and tolerability of dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Cambodia.
2007 Feb
Intermittent preventive treatment for malaria in pregnancy in Africa: what's new, what's needed?
2007 Feb 16
Overestimating resistance in field testing of malaria parasites: simple methods for estimating high EC50 values using a Bayesian approach.
2007 Jan 17
Gene encoding a deubiquitinating enzyme is mutated in artesunate- and chloroquine-resistant rodent malaria parasites.
2007 Jul
Activity of piperaquine and other 4-aminoquinoline antiplasmodial drugs against chloroquine-sensitive and resistant blood-stages of Plasmodium falciparum. Role of beta-haematin inhibition and drug concentration in vacuolar water- and lipid-phases.
2007 Jun 15
In vitro activity of ferroquine (SSR 97193) against Plasmodium falciparum isolates from the Thai-Burmese border.
2007 Jun 27
Large-scale malaria survey in Cambodia: novel insights on species distribution and risk factors.
2007 Mar 27
Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison.
2007 Mar 3
Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment of malaria: a randomized trial.
2007 May 18
Dose ranging studies of new artemisinin-piperaquine fixed combinations compared to standard regimens of artemisisnin combination therapies for acute uncomplicated falciparum malaria.
2007 Nov
Sensitive and rapid liquid chromatography/tandem mass spectrometric assay for the quantification of piperaquine in human plasma.
2007 Nov 1
Pharmacokinetics of piperaquine after single and multiple oral administrations in healthy volunteers.
2007 Oct
A randomised controlled trial to assess the efficacy of dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Peru.
2007 Oct 31
Efficacy and safety of dihydroartemisinin-piperaquine.
2007 Sep
World Antimalarial Resistance Network (WARN) IV: clinical pharmacology.
2007 Sep 6
World Antimalarial Resistance Network (WARN) III: molecular markers for drug resistant malaria.
2007 Sep 6
World Antimalarial Resistance Network (WARN) II: in vitro antimalarial drug susceptibility.
2007 Sep 6
Two years after the Fourth External Review: TDR moves forward with a new vision and strategy.
2008
Dihydroartemisinin-piperaquine rescue treatment of multidrug-resistant Plasmodium falciparum malaria in pregnancy: a preliminary report.
2008 Apr
Pharmacokinetics and metabolism of the antimalarial piperaquine after intravenous and oral single doses to the rat.
2008 Aug
A trial of combination antimalarial therapies in children from Papua New Guinea.
2008 Dec 11
Azithromycin-chloroquine and the intermittent preventive treatment of malaria in pregnancy.
2008 Dec 16
Safety, tolerability, and single- and multiple-dose pharmacokinetics of piperaquine phosphate in healthy subjects.
2008 Feb
Development and validation of a liquid chromatographic-tandem mass spectrometric method for determination of piperaquine in plasma stable isotope labeled internal standard does not always compensate for matrix effects.
2008 Feb 1
Sulfadoxine-pyrimethamine-based combinations for malaria: a randomised blinded trial to compare efficacy, safety and selection of resistance in Malawi.
2008 Feb 13
How antimalarial drug resistance affects post-treatment prophylaxis.
2008 Jan 11
Antimalarial therapy selection for quinolone resistance among Escherichia coli in the absence of quinolone exposure, in tropical South America.
2008 Jul 16
No PfATPase6 S769N mutation found in Plasmodium falciparum isolates from China.
2008 Jul 8
Quantification of the antimalarial piperaquine in plasma.
2008 May
Effect of folate derivatives on the activity of antifolate drugs used against malaria and cancer.
2008 May
Adverse pregnancy outcomes in an area where multidrug-resistant plasmodium vivax and Plasmodium falciparum infections are endemic.
2008 May 1
In vitro assessment of the pharmacodynamic properties of DB75, piperaquine, OZ277 and OZ401 in cultures of Plasmodium falciparum.
2008 Nov
Revisiting the design of phase III clinical trials of antimalarial drugs for uncomplicated Plasmodium falciparum malaria.
2008 Nov 18
A randomized trial to monitor the efficacy and effectiveness by QT-NASBA of artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment and transmission control of uncomplicated Plasmodium falciparum malaria in western Kenya.
2008 Nov 18
Spread of anti-malarial drug resistance: mathematical model with implications for ACT drug policies.
2008 Nov 2
Modelling the impact of artemisinin combination therapy and long-acting treatments on malaria transmission intensity.
2008 Nov 25
Pharmacokinetics of the antimalarial drug piperaquine in healthy Vietnamese subjects.
2008 Oct
A single LC-tandem mass spectrometry method for the simultaneous determination of 14 antimalarial drugs and their metabolites in human plasma.
2009 Apr 1
Mefloquine pharmacokinetics and mefloquine-artesunate effectiveness in Peruvian patients with uncomplicated Plasmodium falciparum malaria.
2009 Apr 9
Plasmodium berghei ANKA: selection of resistance to piperaquine and lumefantrine in a mouse model.
2009 Jul
A randomized, controlled trial of artemisinin-piperaquine vs dihydroartemisinin-piperaquine phosphate in treatment of falciparum malaria.
2009 Jun
Antimalarial drug susceptibility of Plasmodium vivax in the Republic of Korea.
2009 Jun
Antimalarial therapies in children from Papua New Guinea.
2009 Mar 19
Open label randomized comparison of dihydroartemisinin-piperaquine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in central Vietnam.
2009 May
Discovery of dual function acridones as a new antimalarial chemotype.
2009 May 14
A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malaria.
2009 May 4
Patents

Patents

Sample Use Guides

Primaquine (One tablet contains 13.2mg primaquine disphosphate/7.5mg base. Weight based regimen: 0.25mg base/kg) for 14 days
Route of Administration: Oral
he antimalarial susceptibilities of P. ovale and P. malariae isolates were measured using a protocol modified from the WHO microtes Venous blood (5 ml) was collected by venipuncture, and after removal of host white blood cells using a CF11 column, 2 ml of packed infected red blood cells (IRBC) were divided as follows: 1 ml was cryopreserved in glycerolyte, 200 mkl was spotted onto filter paper, and 800 _l was used for the in vitro drug susceptibility assay. Two hundred microliters of a 2% hematocrit blood medium mixture (BMM) consisting of McCoy’s 5A medium. and 20% AB_ human serum was added to each well of predosed drug plates; the drug plates contained 11 serial concentrations (2-fold dilutions) of the antimalarials, with maximum concentrations of 5,910 nM for chloroquine, 557 nM for amodiaquine, 93 nM for artesunate, 338 nM for mefloquine, 87 nM for pyronaradine, and 769 nM for piperaquine. A candle jar was used to mature the parasites at 37.5°C for 15 to 56 h. Incubation was stopped when >40% of ring stage parasites had matured into mature schizonts in the drug-free control. Preliminary studies demonstrated that once the 40% schizont threshold had been reached, further incubation did not increase the final count.
Name Type Language
PIPERAQUINE PHOSPHATE (1:1)
Common Name English
QUINOLINE, 4,4'-(1,3-PROPANEDIYLDI-4,1-PIPERAZINEDIYL)BIS(7-CHLORO-, PHOSPHATE (1:1)
Systematic Name English
Code System Code Type Description
CAS
85547-56-4
Created by admin on Sat Dec 16 15:15:07 GMT 2023 , Edited by admin on Sat Dec 16 15:15:07 GMT 2023
PRIMARY
SMS_ID
100000115441
Created by admin on Sat Dec 16 15:15:07 GMT 2023 , Edited by admin on Sat Dec 16 15:15:07 GMT 2023
PRIMARY
FDA UNII
5A17BAT3GK
Created by admin on Sat Dec 16 15:15:07 GMT 2023 , Edited by admin on Sat Dec 16 15:15:07 GMT 2023
PRIMARY
PUBCHEM
174478
Created by admin on Sat Dec 16 15:15:07 GMT 2023 , Edited by admin on Sat Dec 16 15:15:07 GMT 2023
PRIMARY
EPA CompTox
DTXSID601006108
Created by admin on Sat Dec 16 15:15:07 GMT 2023 , Edited by admin on Sat Dec 16 15:15:07 GMT 2023
PRIMARY