pyrimethamine   Click here for help

GtoPdb Ligand ID: 4800

Synonyms: Daraprim® | GNF-Pf-5586 | TCMDC-125860
Approved drug PDB Ligand Antimalarial Ligand
pyrimethamine is an approved drug (FDA (1953))
Compound class: Synthetic organic
Comment: Pyrimethamine is an antifolate compound with broad-spectrum antiprotozoal activity. It is used in the treatment and prevention of malaria as part of a combination therapy.

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: pyrimethamine

pyrimethamine is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 2
Topological polar surface area 77.82
Molecular weight 248.08
XLogP 2.68
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CCc1nc(N)nc(c1c1ccc(cc1)Cl)N
Isomeric SMILES CCc1nc(N)nc(c1c1ccc(cc1)Cl)N
InChI InChI=1S/C12H13ClN4/c1-2-9-10(11(14)17-12(15)16-9)7-3-5-8(13)6-4-7/h3-6H,2H2,1H3,(H4,14,15,16,17)
InChI Key WKSAUQYGYAYLPV-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Pyrimethamine is used in the treatment of toxoplasmosis and acute malaria. Also used for the prevention of malaria in areas without resistance to pyrimethamine.
Pyrimethamine is listed in the World Health Organisation's EML as a curative treatment for uncomplicated P. falciparum malaria in combination with sulfadoxine and artesunate. This is one of the artemisinin-based combination therapies (ACTs) recommended in the WHO's Guidelines for the treatment of malaria [6]
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Interferes with the formation of malarial schizont in erthrocytes and the liver. This is via the inhibition of the dihydrofolate reductase-thymidylate synthase in plasmodia which blocks the biosynthesis of purines and pyrimidines, leading to failure of nuclear division.
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com