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Details

Stereochemistry RACEMIC
Molecular Formula C24H28F3N3O3.C4H6O4
Molecular Weight 581.5807
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TAFENOQUINE SUCCINATE

SMILES

OC(=O)CCC(O)=O.COC1=NC2=C(NC(C)CCCN)C=C(OC)C(OC3=CC=CC(=C3)C(F)(F)F)=C2C(C)=C1

InChI

InChIKey=CQBKFGJRAOXYIP-UHFFFAOYSA-N
InChI=1S/C24H28F3N3O3.C4H6O4/c1-14-11-20(32-4)30-22-18(29-15(2)7-6-10-28)13-19(31-3)23(21(14)22)33-17-9-5-8-16(12-17)24(25,26)27;5-3(6)1-2-4(7)8/h5,8-9,11-13,15,29H,6-7,10,28H2,1-4H3;1-2H2,(H,5,6)(H,7,8)

HIDE SMILES / InChI

Molecular Formula C24H28F3N3O3
Molecular Weight 463.4926
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Molecular Formula C4H6O4
Molecular Weight 118.088
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Tafenoquine is anti-malaria drug originated in Walter reed army institute of research and developed by GSK and 60 Degrees Pharmaceuticals. In 2018 United States Food and Drug Administration (FDA) approved single dose tafenoquine for the radical cure (prevention of relapse) of Plasmodium vivax malaria. Tafenoquine, an 8-aminoquinoline antimalarial, is active against all the stages of Plasmodium species that include the hypnozoite (dormant stage) in the liver. Studies in vitro with the erythrocytic forms of Plasmodium falciparum suggest that tafenoquine may exert its effect by inhibiting hematin polymerization and inducing apoptotic like death of the parasite. In addition to its effect on the parasite, tafenoquine causes red blood cell shrinkage in vitro. Tafenoquine is active against pre-erythrocytic (liver) and erythrocytic (asexual) forms as well as gametocytes of Plasmodium species that include P. falciparum and P. vivax. The activity of tafenoquine against the pre-erythrocytic liver stages of the parasite, prevents the development of the erythrocytic forms of the parasite.

CNS Activity

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ARAKODA
PubMed

PubMed

TitleDatePubMed
8-Aminoquinolines from Walter Reed Army Institute for Research for treatment and prophylaxis of Pneumocystis pneumonia in rat models.
1991 Feb
Isolation and characterization of rat lung Pneumocystis carinii gp120.
1991 Nov-Dec
8-aminoquinolines effective against Pneumocystis carinii in vitro and in vivo.
1993 Oct
New drug developments for opportunistic infections in immunosuppressed patients: Pneumocystis carinii.
1995 Nov 24
Malaria prophylaxis/radical cure: recent experiences of the Australian Defence Force.
2001
Population pharmacokinetics of the new antimalarial agent tafenoquine in Thai soldiers.
2001 Dec
Development of new drugs for chemoprophylaxis of malaria.
2001 Jul
Rapid determination of tafenoquine in small volume human plasma samples by high-performance liquid chromatography-tandem mass spectrometry.
2002 Mar 25
Triangular test applied to the clinical trial of azithromycin against relapses in Plasmodium vivax infections.
2002 Nov 12
In-vitro interaction of tafenoquine and chloroquine in Plasmodium falciparum from northwestern Thailand.
2003
Stereoselectivity in the pharmacodynamics and pharmacokinetics of the chiral antimalarial drugs.
2003
The chemotherapy of rodent malaria. LXI. Drug combinations to impede the selection of drug resistance, part 4: the potential role of 8-aminoquinolines.
2003 Apr
Military aviators, special operations forces, and causal malaria prophylaxis.
2003 Dec
Plasma concentrations of tafenoquine, a new long-acting antimalarial agent, in thai soldiers receiving monthly prophylaxis.
2003 Dec 15
Efficacy of a 14-day primaquine regimen in preventing relapses in patients with Plasmodium vivax malaria in Mumbai, India.
2003 Jul-Aug
Molecule of the month. Tafenoquine succinate.
2003 May
Transmission-blocking activity of tafenoquine (WR-238605) and artelinic acid against naturally circulating strains of Plasmodium vivax in Thailand.
2003 Nov
Malaria chemoprophylaxis: when should we use it and what are the options?
2004 Feb
Randomized trial of 3-dose regimens of tafenoquine (WR238605) versus low-dose primaquine for preventing Plasmodium vivax malaria relapse.
2004 Oct 15
Efficacy of monthly tafenoquine for prophylaxis of Plasmodium vivax and multidrug-resistant P. falciparum malaria.
2004 Oct 15
Modern malaria chemoprophylaxis.
2005
[Malaria chemoprophylaxis in traveling children].
2005 Jan
Treatment of acute vivax malaria with tafenoquine.
2005 Jan
New strategies for the prevention of malaria in travelers.
2005 Mar
Drug development papers in PLoS Medicine: how we try to spot a winner.
2006 Dec
A plant-derived morphinan as a novel lead compound active against malaria liver stages.
2006 Dec
8-Aminoquinolines: future role as antiprotozoal drugs.
2006 Dec
Antimalarial efficacy and drug interactions of the novel semi-synthetic endoperoxide artemisone in vitro and in vivo.
2007 Apr
Intermittent preventive treatment for malaria in pregnancy in Africa: what's new, what's needed?
2007 Feb 16
Tafenoquine for the treatment of recurrent Plasmodium vivax malaria.
2007 Mar
Gender differences in gastrointestinal disturbances and plasma concentrations of tafenoquine in healthy volunteers after tafenoquine administration for post-exposure vivax malaria prophylaxis.
2007 Mar
Tafenoquine: a promising new antimalarial agent.
2007 May
Selective plasma protein binding of antimalarial drugs to alpha1-acid glycoprotein.
2008 Apr 1
Prevalence of contraindications to mefloquine use among USA military personnel deployed to Afghanistan.
2008 Feb 11
Glucose-6-phosphate dehydrogenase deficiency in an endemic area for malaria in Manaus: a cross-sectional survey in the Brazilian Amazon.
2009
In vitro activity of pyronaridine against Plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays.
2009 Apr 23
A randomized, double-blind, safety and tolerability study to assess the ophthalmic and renal effects of tafenoquine 200 mg weekly versus placebo for 6 months in healthy volunteers.
2009 Aug
Effects of mefloquine and artesunate mefloquine on the emergence, clearance and sex ratio of Plasmodium falciparum gametocytes in malarious children.
2009 Dec 16
Visualisation and quantitative analysis of the rodent malaria liver stage by real time imaging.
2009 Nov 18
Structural modifications of quinoline-based antimalarial agents: Recent developments.
2010 Apr
Antileishmanial and antitrypanosomal activities of the 8-aminoquinoline tafenoquine.
2010 Dec
Anti-malarial drugs and the prevention of malaria in the population of malaria endemic areas.
2010 Dec 13
Establishment of an in vitro assay for assessing the effects of drugs on the liver stages of Plasmodium vivax malaria.
2010 Dec 9
Gateways to clinical trials.
2010 Jun
In vitro selection of Plasmodium falciparum drug-resistant parasite lines.
2010 Mar
Efficacy and safety of chloroquine for treatment in patients with uncomplicated Plasmodium vivax infections in endemic countries.
2010 Nov
Operational strategies to achieve and maintain malaria elimination.
2010 Nov 6
Anti-bacterial activity of intermittent preventive treatment of malaria in pregnancy: comparative in vitro study of sulphadoxine-pyrimethamine, mefloquine, and azithromycin.
2010 Oct 29
A SYBR Green 1-based in vitro test of susceptibility of Ghanaian Plasmodium falciparum clinical isolates to a panel of anti-malarial drugs.
2013 Dec 17
Patents

Patents

Sample Use Guides

In Vivo Use Guide
Loading regimen: 200 mg (2 of the 100 mg tablets) once daily for 3 days Maintenance regimen: 200 mg (2 of the 100 mg tablets) once weekly – start 7 days after the last loading regimen dose Terminal prophylaxis regimen: 200 mg (2 of the 100 mg tablets) one-time 7 days after the last maintenance dose
Route of Administration: Oral
In Vitro Use Guide
After 72 h of tafenoquine exposure, proliferation of L. donovani and Leishmania major promastigotes was inhibited at the micromolar range in a dose-dependent manner, with 50% effective concentrations (EC50s) of 5.6 ± 1.0 uM and 5.3 ± 2.1 uM for L. donovani.
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:11:58 UTC 2019
Edited
by admin
on Mon Oct 21 20:11:58 UTC 2019
Record UNII
DL5J0B8VSS
Record Status Validated (UNII)
Record Version
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Name Type Language
TAFENOQUINE SUCCINATE
MI   USAN  
USAN  
Official Name English
BUTANEDIOIC ACID, COMPD. WITH N4-(2,6-DIMETHOXY-4-METHYL-5-(3-(TRIFLUOROMETHYL)PHENOXY)-8-QUINOLINYL)-1,4-PENTANEDIAMINE (1:1)
Common Name English
WR-238605
Code English
(4RS)-N4-(2,6-DIMETHOXY-4-METHYL-5-(3-(TRIFLUOROMETHYL)PHENOXY)QUINOLIN-8-YL)PENTANE-1,4-DIAMINE BUTANEDIOATE
Systematic Name English
KRINTAFEL
Brand Name English
TAFENOQUINE SUCCINATE [WHO-DD]
Common Name English
TAFENOQUINE SUCCINATE [USAN]
Common Name English
TAFENOQUINE SUCCINATE [MI]
Common Name English
ARAKODA
Brand Name English
SB-252263-AX
Code English
Classification Tree Code System Code
NCI_THESAURUS C271
Created by admin on Mon Oct 21 20:11:58 UTC 2019 , Edited by admin on Mon Oct 21 20:11:58 UTC 2019
Code System Code Type Description
NCI_THESAURUS
C152489
Created by admin on Mon Oct 21 20:11:58 UTC 2019 , Edited by admin on Mon Oct 21 20:11:58 UTC 2019
PRIMARY
CAS
106635-81-8
Created by admin on Mon Oct 21 20:11:58 UTC 2019 , Edited by admin on Mon Oct 21 20:11:58 UTC 2019
PRIMARY
MERCK INDEX
M10429
Created by admin on Mon Oct 21 20:11:58 UTC 2019 , Edited by admin on Mon Oct 21 20:11:58 UTC 2019
PRIMARY Merck Index
ChEMBL
CHEMBL298470
Created by admin on Mon Oct 21 20:11:58 UTC 2019 , Edited by admin on Mon Oct 21 20:11:58 UTC 2019
PRIMARY
PUBCHEM
163761
Created by admin on Mon Oct 21 20:11:58 UTC 2019 , Edited by admin on Mon Oct 21 20:11:58 UTC 2019
PRIMARY
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PARENT -> SALT/SOLVATE