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

Molecular Formula	C29H32ClN5O2
Molecular Weight	518.05
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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
[Study on treatment of multi-drug resistant falciparum malaria by using a combination of dihydroartemisinin and pyronaridine].	2002	12568014
[Factors affecting the in vitro microtest for drug sensitivity of Plasmodium falciparum].	2003	14628378
Determination of pyronaridine in whole blood by automated solid phase extraction and high-performance liquid chromatography.	2003 Jun	12766551
New antimalarial drugs.	2003 Nov 10	14613157
Liquid chromatographic determination of pyronaridine in human plasma and oral dosage form.	2003 Oct 5	14522031
Selection and reversal of Plasmodium berghei resistance in the mouse model following repeated high doses of artemether.	2004 Feb	14677058
[[1]Benzothieno[3,2-b]pyridin-4-yl-amine--synthesis and investigation of activity against malaria].	2004 Jul	15297995
Pyronaridine, a novel modulator of P-glycoprotein-mediated multidrug resistance in tumor cells in vitro and in vivo.	2004 Jul 9	15194484
[[1]Benzofuro[3,2-b]pyridin-4-yl-amines - synthesis and investigation of activity against malaria].	2004 Jun	15248458
[Thieno[2,3-c]quinolines - synthesis and biological investigation].	2004 Jun	15248457
Infectious reservoir of Plasmodium infection in Mae Hong Son Province, north-west Thailand.	2004 Sep 22	15385050
Artemisinin-based combination therapies for uncomplicated malaria.	2005 Feb 21	15720175
Chemosusceptibility analysis of Plasmodium falciparum imported malaria in Italy.	2005 Jun	15964498
ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal.	2005 Oct 4	16202168
Concurrence of Plasmodium falciparum dhfr and crt mutations in northern Ghana.	2005 Sep 15	16164748
A new and simple solid-phase extraction method for LC determination of pyronaridine in human plasma.	2005 Sep 25	16046285
[Thieno[3,2-c]quinoline-4-yl-amines--synthesis and investigation of activity against malaria].	2006 Apr	16649537
[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
Treatment of falciparum malaria in the age of drug resistance.	2006 Oct-Dec	17102546
Potentiation of antimalarial drug action by chlorpheniramine against multidrug-resistant Plasmodium falciparum in vitro.	2006 Sep	16750932
Rapid dissemination of Plasmodium falciparum drug resistance despite strictly controlled antimalarial use.	2007 Jan 3	17206274
The role of anti-malarial drugs in eliminating malaria.	2008 Dec 11	19091042
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
Plasmodium vivax trophozoites insensitive to chloroquine.	2008 May 27	18505560
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
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
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
[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
Male and female Plasmodium falciparum mature gametocytes show different responses to antimalarial drugs.	2013 Jul	23629698

Patents

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:25:19 GMT 2023` Edited by `admin` on `Fri Dec 15 16:25:19 GMT 2023`
Record UNII	TD3P7Q3SG6
Record Status	`Validated (UNII)`
Record Version

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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