U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C29H32Cl2N6
Molecular Weight 535.511
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PIPERAQUINE

SMILES

ClC1=CC2=NC=CC(N3CCN(CCCN4CCN(CC4)C5=C6C=CC(Cl)=CC6=NC=C5)CC3)=C2C=C1

InChI

InChIKey=UCRHFBCYFMIWHC-UHFFFAOYSA-N
InChI=1S/C29H32Cl2N6/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/h2-9,20-21H,1,10-19H2

HIDE SMILES / InChI

Molecular Formula C29H32Cl2N6
Molecular Weight 535.511
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
578.47 ng/mL
640 mg single, oral
dose: 640 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PIPERAQUINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
44293 ng × h/mL
640 mg single, oral
dose: 640 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PIPERAQUINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
317.2 h
640 mg single, oral
dose: 640 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PIPERAQUINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
unknown, unknown
PIPERAQUINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
PubMed

PubMed

TitleDatePubMed
Plasmodium berghei ANKA: selection of resistance to piperaquine and lumefantrine in a mouse model.
2009-07
A randomized, controlled trial of artemisinin-piperaquine vs dihydroartemisinin-piperaquine phosphate in treatment of falciparum malaria.
2009-06
Antimalarial drug susceptibility of Plasmodium vivax in the Republic of Korea.
2009-06
Discovery of dual function acridones as a new antimalarial chemotype.
2009-05-14
A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malaria.
2009-05-04
Open label randomized comparison of dihydroartemisinin-piperaquine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in central Vietnam.
2009-05
Mefloquine pharmacokinetics and mefloquine-artesunate effectiveness in Peruvian patients with uncomplicated Plasmodium falciparum malaria.
2009-04-09
Quantification of artemisinin in human plasma using liquid chromatography coupled to tandem mass spectrometry.
2009-04-05
A single LC-tandem mass spectrometry method for the simultaneous determination of 14 antimalarial drugs and their metabolites in human plasma.
2009-04-01
Disruption of a Plasmodium falciparum multidrug resistance-associated protein (PfMRP) alters its fitness and transport of antimalarial drugs and glutathione.
2009-03-20
Antimalarial therapies in children from Papua New Guinea.
2009-03-19
The last man standing is the most resistant: eliminating artemisinin-resistant malaria in Cambodia.
2009-02-20
Does artesunate prolong the electrocardiograph QT interval in patients with severe malaria?
2009-01
Loss of population levels of immunity to malaria as a result of exposure-reducing interventions: consequences for interpretation of disease trends.
2009
Azithromycin-chloroquine and the intermittent preventive treatment of malaria in pregnancy.
2008-12-16
The role of anti-malarial drugs in eliminating malaria.
2008-12-11
A trial of combination antimalarial therapies in children from Papua New Guinea.
2008-12-11
Modelling the impact of artemisinin combination therapy and long-acting treatments on malaria transmission intensity.
2008-11-25
Revisiting the design of phase III clinical trials of antimalarial drugs for uncomplicated Plasmodium falciparum malaria.
2008-11-18
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.
2008-11-18
Spread of anti-malarial drug resistance: mathematical model with implications for ACT drug policies.
2008-11-02
In vitro assessment of the pharmacodynamic properties of DB75, piperaquine, OZ277 and OZ401 in cultures of Plasmodium falciparum.
2008-11
Pharmacokinetics of the antimalarial drug piperaquine in healthy Vietnamese subjects.
2008-10
Clinical development of new prophylactic antimalarial drugs after the 5th Amendment to the Declaration of Helsinki.
2008-08
The influence of food on the pharmacokinetics of piperaquine in healthy Vietnamese volunteers.
2008-08
Pharmacokinetics and metabolism of the antimalarial piperaquine after intravenous and oral single doses to the rat.
2008-08
Antimalarial therapy selection for quinolone resistance among Escherichia coli in the absence of quinolone exposure, in tropical South America.
2008-07-16
Toxicology and pharmacokinetics of piperaquine in mice.
2008-07-10
No PfATPase6 S769N mutation found in Plasmodium falciparum isolates from China.
2008-07-08
Quality control of piperaquine in pharmaceutical formulations by capillary zone electrophoresis.
2008-06-30
Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda.
2008-06-11
Plasmodium vivax trophozoites insensitive to chloroquine.
2008-05-27
Adverse pregnancy outcomes in an area where multidrug-resistant plasmodium vivax and Plasmodium falciparum infections are endemic.
2008-05-01
Quantification of the antimalarial piperaquine in plasma.
2008-05
Effect of folate derivatives on the activity of antifolate drugs used against malaria and cancer.
2008-05
Dihydroartemisinin-piperaquine rescue treatment of multidrug-resistant Plasmodium falciparum malaria in pregnancy: a preliminary report.
2008-04
[Efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine in the treatment of uncomplicated falciparum malaria in Hainan, China].
2008-02-28
Sulfadoxine-pyrimethamine-based combinations for malaria: a randomised blinded trial to compare efficacy, safety and selection of resistance in Malawi.
2008-02-13
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.
2008-02-01
Safety, tolerability, and single- and multiple-dose pharmacokinetics of piperaquine phosphate in healthy subjects.
2008-02
How antimalarial drug resistance affects post-treatment prophylaxis.
2008-01-11
Efficacy of Artequick versus artesunate-mefloquine in the treatment of acute uncomplicated falciparum malaria in Thailand.
2008-01
Two years after the Fourth External Review: TDR moves forward with a new vision and strategy.
2008
Intermittent preventive treatment for the prevention of malaria during pregnancy in high transmission areas.
2007-12-04
Randomized comparison of amodiaquine plus sulfadoxine-pyrimethamine, artemether-lumefantrine, and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso.
2007-12-01
Sensitive and rapid liquid chromatography/tandem mass spectrometric assay for the quantification of piperaquine in human plasma.
2007-11-01
Dose ranging studies of new artemisinin-piperaquine fixed combinations compared to standard regimens of artemisisnin combination therapies for acute uncomplicated falciparum malaria.
2007-11
A randomised controlled trial to assess the efficacy of dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Peru.
2007-10-31
Pharmacokinetics of piperaquine after single and multiple oral administrations in healthy volunteers.
2007-10
World Antimalarial Resistance Network (WARN) IV: clinical pharmacology.
2007-09-06
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.
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:16:46 GMT 2025
Edited
by admin
on Mon Mar 31 18:16:46 GMT 2025
Record UNII
A0HV2Q956Y
Record Status Validated (UNII)
Record Version
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Name Type Language
PIPERAQUINOLINE
Preferred Name English
PIPERAQUINE
WHO-DD  
Common Name English
QUINOLINE, 4,4'-(TRIMETHYLENEDI-4,1-PIPERAZINEDIYL)BIS(7-CHLORO-
Systematic Name English
Piperaquine [WHO-DD]
Common Name English
QUINOLINE, 4,4'-(1,3-PROPANEDIYLDI-4,1-PIPERAZINEDIYL)BIS(7-CHLORO-
Systematic Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 234006
Created by admin on Mon Mar 31 18:16:46 GMT 2025 , Edited by admin on Mon Mar 31 18:16:46 GMT 2025
WHO-ATC P01BX02
Created by admin on Mon Mar 31 18:16:46 GMT 2025 , Edited by admin on Mon Mar 31 18:16:46 GMT 2025
EU-Orphan Drug EU/3/07/468
Created by admin on Mon Mar 31 18:16:46 GMT 2025 , Edited by admin on Mon Mar 31 18:16:46 GMT 2025
NCI_THESAURUS C271
Created by admin on Mon Mar 31 18:16:46 GMT 2025 , Edited by admin on Mon Mar 31 18:16:46 GMT 2025
WHO-ATC P01BF05
Created by admin on Mon Mar 31 18:16:46 GMT 2025 , Edited by admin on Mon Mar 31 18:16:46 GMT 2025
Code System Code Type Description
MESH
C034759
Created by admin on Mon Mar 31 18:16:46 GMT 2025 , Edited by admin on Mon Mar 31 18:16:46 GMT 2025
PRIMARY
PUBCHEM
122262
Created by admin on Mon Mar 31 18:16:46 GMT 2025 , Edited by admin on Mon Mar 31 18:16:46 GMT 2025
PRIMARY
EPA CompTox
DTXSID00193825
Created by admin on Mon Mar 31 18:16:46 GMT 2025 , Edited by admin on Mon Mar 31 18:16:46 GMT 2025
PRIMARY
EVMPD
SUB179557
Created by admin on Mon Mar 31 18:16:46 GMT 2025 , Edited by admin on Mon Mar 31 18:16:46 GMT 2025
PRIMARY
DRUG BANK
DB13941
Created by admin on Mon Mar 31 18:16:46 GMT 2025 , Edited by admin on Mon Mar 31 18:16:46 GMT 2025
PRIMARY
SMS_ID
100000164921
Created by admin on Mon Mar 31 18:16:46 GMT 2025 , Edited by admin on Mon Mar 31 18:16:46 GMT 2025
PRIMARY
CAS
4085-31-8
Created by admin on Mon Mar 31 18:16:46 GMT 2025 , Edited by admin on Mon Mar 31 18:16:46 GMT 2025
PRIMARY
WIKIPEDIA
PIPERAQUINE
Created by admin on Mon Mar 31 18:16:46 GMT 2025 , Edited by admin on Mon Mar 31 18:16:46 GMT 2025
PRIMARY
FDA UNII
A0HV2Q956Y
Created by admin on Mon Mar 31 18:16:46 GMT 2025 , Edited by admin on Mon Mar 31 18:16:46 GMT 2025
PRIMARY
NCI_THESAURUS
C87634
Created by admin on Mon Mar 31 18:16:46 GMT 2025 , Edited by admin on Mon Mar 31 18:16:46 GMT 2025
PRIMARY
DRUG CENTRAL
4193
Created by admin on Mon Mar 31 18:16:46 GMT 2025 , Edited by admin on Mon Mar 31 18:16:46 GMT 2025
PRIMARY
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC administered alone

in Healthy Adult Thai Subjects