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
Guide to Malaria Pharmacology Comments
Pyrimethamine was developed at the beginning of the 1950s and was part of the work that led to the 1988 Nobel Prize in Physiology or Medicine being awarded to Gertrude Elion and George Hitchings for their discoveries of "important principles for drug treatment" [3]. Resistance to the antifolate class of antimalarial drugs, including pyrimethamine, emerged soon after their clinical introduction and arisies from mutations in PfDHFR-TS [4].

Potential Target/Mechanism Of Action: Pyrimethamine inhibits Plasmodium dihydrofolate reductase-thymidylate synthase (DHFR-TS).