PYRONARIDINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C29H32ClN5O2
Molecular Weight	518.05
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=NC2=C(NC3=CC(CN4CCCC4)=C(O)C(CN5CCCC5)=C3)C6=CC=C(Cl)C=C6N=C2C=C1

InChI

InChIKey=DJUFPMUQJKWIJB-UHFFFAOYSA-N

InChI=1S/C29H32ClN5O2/c1-37-26-9-8-24-28(33-26)27(23-7-6-21(30)16-25(23)32-24)31-22-14-19(17-34-10-2-3-11-34)29(36)20(15-22)18-35-12-4-5-13-35/h6-9,14-16,36H,2-5,10-13,17-18H2,1H3,(H,31,32)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22877082 | https://www.ncbi.nlm.nih.gov/pubmed/14613157 | https://www.mmv.org/access/products-projects/pyramax-pyronaridine-artesunate

Pyronaridine was developed in China and has been registered in that country since the 1980s. Outside China, none of the existing formulations is registered because of the failure to meet international regulatory standards. Pyronaridine is generally active against chloroquine-resistant parasites. Pyronaridine has been investigated for the treatment of Malaria. Pyronaridine targets hematin. Combination of pyronaridine with artesunate was indicated for the blood-stage treatment of both strains of malaria:  P. falciparum and P. vivax.  WHO currently recommends artesunate-pyronaridine in areas where other artemisinin-based combination therapies are failing.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
hematin 2 Target ID: hematin Sources: https://www.ncbi.nlm.nih.gov/pubmed/16723583	Inhibitor 8297

PubMed

Title	Date	PubMed
[Establishment of in vitro microtest for determining sensitivity of Plasmodium falciparum to pyronaridine].	2006 Apr 30	16862905
Activity of azithromycin or erythromycin in combination with antimalarial drugs against multidrug-resistant Plasmodium falciparum in vitro.	2006 Dec	17126280
Determination of the physicochemical properties of pyronaridine - a new antimalarial drug.	2006 Jan	16632444
Antimalarial activity of concanamycin A alone and in combination with pyronaridine.	2006 Jul	17121284
Potentiation of anti-epileptic drugs effectiveness by pyronaridine in refractory epilepsy.	2007	17368747
[Benzo[c][2,7]naphthyridine-5-yl-arylamines-phenol Mannich bases of the amodiaquine-, cycloquine- and pyronaridine-type].	2007 Feb	17341024
Overestimating resistance in field testing of malaria parasites: simple methods for estimating high EC50 values using a Bayesian approach.	2007 Jan 17	17229314
Rapid dissemination of Plasmodium falciparum drug resistance despite strictly controlled antimalarial use.	2007 Jan 3	17206274
Development and validation of a liquid chromatography-mass spectrometry assay for the determination of pyronaridine in human urine.	2007 Jun 15	17409032
Geometric least squares means ratios for the analysis of Plasmodium falciparum in vitro susceptibility to antimalarial drugs.	2007 Nov 26	18039388
Development and validation of a liquid chromatography-mass spectrometry assay for the determination of pyronaridine in human blood for application to clinical pharmacokinetic studies.	2007 Sep 21	17681448
World Antimalarial Resistance Network (WARN) IV: clinical pharmacology.	2007 Sep 6	17822537
World Antimalarial Resistance Network (WARN) II: in vitro antimalarial drug susceptibility.	2007 Sep 6	17822533
The role of anti-malarial drugs in eliminating malaria.	2008 Dec 11	19091042
Azithromycin-chloroquine and the intermittent preventive treatment of malaria in pregnancy.	2008 Dec 16	19087267
Sulfadoxine-pyrimethamine-based combinations for malaria: a randomised blinded trial to compare efficacy, safety and selection of resistance in Malawi.	2008 Feb 13	18270569
How antimalarial drug resistance affects post-treatment prophylaxis.	2008 Jan 11	18186948
Antimalarial therapy selection for quinolone resistance among Escherichia coli in the absence of quinolone exposure, in tropical South America.	2008 Jul 16	18648533
No PfATPase6 S769N mutation found in Plasmodium falciparum isolates from China.	2008 Jul 8	18606023
Anti-malarial efficacy of pyronaridine and artesunate in combination in vitro and in vivo.	2008 Mar	18279817
Effect of folate derivatives on the activity of antifolate drugs used against malaria and cancer.	2008 May	18259776
Plasmodium vivax trophozoites insensitive to chloroquine.	2008 May 27	18505560
Fixed-dose pyronaridine-artesunate combination for treatment of uncomplicated falciparum malaria in pediatric patients in Gabon.	2008 Sep 15	18694333
Mefloquine--an aminoalcohol with promising antischistosomal properties in mice.	2009	19125172
A single LC-tandem mass spectrometry method for the simultaneous determination of 14 antimalarial drugs and their metabolites in human plasma.	2009 Apr 1	19249251
In vitro activity of pyronaridine against Plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays.	2009 Apr 23	19389221
Residual antimalarials in malaria patients from Tanzania--implications on drug efficacy assessment and spread of parasite resistance.	2009 Dec 14	20011529
Population pharmacokinetics of artesunate and dihydroartemisinin following single- and multiple-dosing of oral artesunate in healthy subjects.	2009 Dec 18	20021657
Plasmodium berghei ANKA: selection of resistance to piperaquine and lumefantrine in a mouse model.	2009 Jul	19318094
A comparative, randomized clinical trial of artemisinin/naphtoquine twice daily one day versus artemether/lumefantrine six doses regimen in children and adults with uncomplicated falciparum malaria in Côte d'Ivoire.	2009 Jul 3	19575797
The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum.	2009 Mar 16	19291301
Field-adapted sampling of whole blood to determine the levels of amodiaquine and its metabolite in children with uncomplicated malaria treated with amodiaquine plus artesunate combination.	2009 Mar 30	19331684
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	19413906
Synergism between pyronaridine and retinol in Plasmodium falciparum in vitro.	2009 Oct	19915814
Simple field assays to check quality of current artemisinin-based antimalarial combination formulations.	2009 Sep 30	19789707
Absorption, distribution, excretion, and pharmacokinetics of 14C-pyronaridine tetraphosphate in male and female Sprague-Dawley rats.	2010	20379367
Intermittent preventive treatment in infants for the prevention of malaria in rural Western kenya: a randomized, double-blind placebo-controlled trial.	2010 Apr 2	20368815
Sustainable development of a GCP-compliant clinical trials platform in Africa: the malaria clinical trials alliance perspective.	2010 Apr 20	20406478
Efficacy and safety of a fixed-dose oral combination of pyronaridine-artesunate compared with artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria: a randomised non-inferiority trial.	2010 Apr 24	20417857
Pyronaridine-artesunate for uncomplicated falciparum malaria.	2010 Apr 24	20417841
Antimalarial drug targets in Plasmodium falciparum predicted by stage-specific metabolic network analysis.	2010 Aug 31	20807400
In vitro activity of pyronaridine against multidrug-resistant Plasmodium falciparum and Plasmodium vivax.	2010 Dec	20876370
Adolescence as risk factor for adverse pregnancy outcome in Central Africa--a cross-sectional study.	2010 Dec 20	21188301
In vitro susceptibility of Plasmodium falciparum isolates from Abidjan, Côte d'Ivoire, to artemisinin, chloroquine, dihydroartemisinin and pyronaridine.	2010 Jan	20737832
[A new antimalarial drug combination].	2010 May 5	20499586
Absence of association between pyronaridine in vitro responses and polymorphisms in genes involved in quinoline resistance in Plasmodium falciparum.	2010 Nov 25	21108786
Synergism between pyronaridine and retinol in Plasmodium vivax in vitro.	2010 Oct	20924697
In vitro activity of antiretroviral drugs against Plasmodium falciparum.	2011 Nov	21876053
Baseline in vitro activities of the antimalarials pyronaridine and methylene blue against Plasmodium falciparum isolates from Kenya.	2012 Feb	22123687
Male and female Plasmodium falciparum mature gametocytes show different responses to antimalarial drugs.	2013 Jul	23629698

Patents

Name

Type

Language

PYRONARIDINE

Official Name

English

4-((7-CHLORO-2-METHOXYBENZO(B)-1,5-NAPHTHYRIDIN-10-YL)AMINO)-2,6-BIS(1-PYRROLIDINYLMETHYL)PHENOL

Systematic Name

English

pyronaridine [INN]

Common Name

English

4-((7-CHLORO-2-METHOXYBENZO(B)(1,5)NAPHTHYRIDIN-10-YL)AMINO)-2,6-BIS((PYRROLIDIN-1-YL)METHYL)PHENOL

Systematic Name

English

PYRONARIDINE [MI]

Common Name

English

Pyronaridine [WHO-DD]

Common Name

English

MALARIDINE

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

696919