pyrimethamine   

GtoPdb Ligand ID: 4800

Synonyms: Daraprim® | GNF-Pf-5586 | TCMDC-125860
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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2D Structure
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Physico-chemical Properties
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
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
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 21st Essential Medicines List (2019) 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
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.
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