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
References
1. Delves M, Plouffe D, Scheurer C, Meister S, Wittlin S, Winzeler EA, Sinden RE, Leroy D. (2012)
The activities of current antimalarial drugs on the life cycle stages of Plasmodium: a comparative study with human and rodent parasites.
PLoS Med., 9 (2): e1001169. [PMID:22363211]
2. Ito S, Kusuhara H, Kuroiwa Y, Wu C, Moriyama Y, Inoue K, Kondo T, Yuasa H, Nakayama H, Horita S et al.. (2010)
Potent and specific inhibition of mMate1-mediated efflux of type I organic cations in the liver and kidney by pyrimethamine.
J. Pharmacol. Exp. Ther., 333 (1): 341-50. [PMID:20065018]
3. Nobel Media AB 2019. 
Press release. The Nobel Prize in Physiology or Medicine 1988.
Accessed on 16/07/2019. Modified on 16/07/2019. NobelPrize.org, https://www.nobelprize.org/prizes/medicine/1988/press-release/
4. Sirawaraporn W, Sathitkul T, Sirawaraporn R, Yuthavong Y, Santi DV. (1997)
Antifolate-resistant mutants of Plasmodium falciparum dihydrofolate reductase.
Proc. Natl. Acad. Sci. U.S.A., 94 (4): 1124-9. [PMID:9037017]
5. Yuthavong Y, Tarnchompoo B, Vilaivan T, Chitnumsub P, Kamchonwongpaisan S, Charman SA, McLennan DN, White KL, Vivas L, Bongard E et al.. (2012)
Malarial dihydrofolate reductase as a paradigm for drug development against a resistance-compromised target.
Proc. Natl. Acad. Sci. U.S.A., 109 (42): 16823-8. [PMID:23035243]
6. (2015)
Treatment of uncomplicated Plasmodium falciparum malaria.  In  Guidelines for the Treatment of Malaria. Third edition. (World Health Organization) . [PMID:26020088] [ISBN:9789241549127]