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Record Information
Version3.6
Creation Date2012-09-06 15:16:49 UTC
Update Date2013-02-09 00:31:19 UTC
HMDB IDHMDB14350
Secondary Accession NumbersNone
Metabolite Identification
Common NamePyrimethamine
DescriptionPyrimethamine is only found in individuals that have used or taken this drug. It is one of the folic acid antagonists that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis. [PubChem]Pyrimethamine inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are essential for DNA synthesis and cell multiplication. This leads to failure of nuclear division at the time of schizont formation in erythrocytes and liver.
Structure
Thumb
Synonyms
  1. CD
  2. Chloridin
  3. Chloridine
  4. Chloridyn
  5. Diaminopyritamin
  6. Ethylpyrimidine
  7. Pirimetamin
  8. Pirimetamina
  9. Primethamine
  10. Pyremethamine
  11. Pyrimethamin
Chemical FormulaC12H13ClN4
Average Molecular Weight248.711
Monoisotopic Molecular Weight248.082874143
IUPAC Name5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine
Traditional IUPAC Namepyrimethamine
CAS Registry Number58-14-0
SMILES
CCC1=C(C(N)=NC(N)=N1)C1=CC=C(Cl)C=C1
InChI Identifier
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 KeyWKSAUQYGYAYLPV-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAromatic Heteropolycyclic Compounds
ClassDiazines
Sub ClassPyrimidines and Pyrimidine Derivatives
Other Descriptors
  • Aromatic Heteropolycyclic Compounds
  • Chlorobenzenes
  • Pyrimidines and Pyrimidine Derivatives
  • aminopyrimidine(ChEBI)
Substituents
  • Aryl Chloride
  • Organochloride
  • Polyamine
Direct ParentAminopyrimidines and Derivatives
Ontology
StatusExpected and Not Quantified
Origin
  • Drug
Biofunction
  • Antimalarials
  • Antiprotozoal Agents
  • Antiprotozoals
  • Folic Acid Antagonists
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point233.5 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility1.79e-01 g/LNot Available
LogP2.7Not Available
Predicted Properties
PropertyValueSource
water solubility0.18 g/LALOGPS
logP2.62ALOGPS
logP2.75ChemAxon
logS-3.1ALOGPS
pKa (strongest acidic)17.22ChemAxon
pKa (strongest basic)7.77ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count2ChemAxon
polar surface area77.82ChemAxon
rotatable bond count2ChemAxon
refractivity71.54ChemAxon
polarizability25.79ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00205
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00205
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00205
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4819
KEGG Compound IDC07391
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkPyrimethamine
NuGOwiki LinkHMDB14350
Metagene LinkHMDB14350
METLIN IDNot Available
PubChem Compound4993
PDB IDCP6
ChEBI ID8673
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Sirichaiwat C, Intaraudom C, Kamchonwongpaisan S, Vanichtanankul J, Thebtaranonth Y, Yuthavong Y: Target guided synthesis of 5-benzyl-2,4-diamonopyrimidines: their antimalarial activities and binding affinities to wild type and mutant dihydrofolate reductases from Plasmodium falciparum. J Med Chem. 2004 Jan 15;47(2):345-54. Pubmed: 14711307
  2. Gatton ML, Martin LB, Cheng Q: Evolution of resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum. Antimicrob Agents Chemother. 2004 Jun;48(6):2116-23. Pubmed: 15155209

Enzymes

General function:
Involved in dihydrofolate reductase activity
Specific function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.
Gene Name:
DHFR
Uniprot ID:
P00374
Molecular weight:
21452.61
References
  1. Rastelli G, Pacchioni S, Parenti MD: Structure of Plasmodium vivax dihydrofolate reductase determined by homology modeling and molecular dynamics refinement. Bioorg Med Chem Lett. 2003 Oct 6;13(19):3257-60. Pubmed: 12951104
  2. Fidock DA, Wellems TE: Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10931-6. Pubmed: 9380737
  3. Wooden JM, Hartwell LH, Vasquez B, Sibley CH: Analysis in yeast of antimalaria drugs that target the dihydrofolate reductase of Plasmodium falciparum. Mol Biochem Parasitol. 1997 Mar;85(1):25-40. Pubmed: 9108546
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed: 11752352
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed: 19934256
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed: 19934256
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular weight:
55824.275
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed: 19934256