5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine

• ChemBase ID: 90
• Molecular Formular: C12H13ClN4
• Molecular Mass: 248.71142
• Monoisotopic Mass: 248.08287412
• SMILES: Clc1ccc(c2c(nc(nc2N)N)CC)cc1
• Canonical 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)
• InChIKey: WKSAUQYGYAYLPV-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine
• IUPAC Traditional name: pyrimethamine
• Brand Name: Darachlor; Daraclor; Darapram; Daraprim; Daraprime; Disulone; Erbaprelina; Fansidar; Khloridin; Malacid; Malocid; Malocide; Maloprim; Pirimecidan; Tindurin; Tinduring
• Synonyms: 2,4-Diamino-5-(4-chlorophenyl)-6-ethylpyrimidine; Khloridin; Pirimetmin; NSC 3061; RP 4753; Pyrimethamine; Daraprim; Malocide; Pirimecidan; 5-(4-Chlorophenyl)-6-ethyl-2,4-pyrimidinediamine; 5-[4-Chlorophenyl]-6-ethyl-2,4-pyrimidinediamine; Pirimetamin; Chloridyn; Pyrimethamine; Pyrimethamine Hcl; Pyrimethamin; Pyremethamine; Ethylpyrimidine; Diaminopyritamin; CD; Chloridin; Chloridine; Primethamine; Pirimetamina; 5-(4-Chlorophenyl)-6-ethylpyriMidine-2,4-diaMine; 6-乙基-5-(4-氯苯基)-2,4-嘧啶二胺; 乙胺嘧啶

Database IDs

• CAS Number: 58-14-0
• EC Number: 200-364-2
• MDL Number: MFCD00057350
• Beilstein Number: 219864
• PubChem SID: 160963553; 24870381; 46505987; 24898876
• PubChem CID: 4993
• CHEBI ID: 8673
• ATC CODE: P01BD01
• CHEMBL: 36
• Chemspider ID: 4819
• DrugBank ID: DB00205
• KEGG ID: D00488
• Unique Ingredient Identifier: Z3614QOX8W
• Wikipedia Title: Pyrimethamine
• Medline Plus: a601050

CALCULATED PROPERTIES

JChem

• Acid pKa: 17.222044
• H Acceptors: 4
• H Donor: 2
• LogD (pH = 5.5): 0.9725773
• LogD (pH = 7.4): 2.2334282
• Log P: 2.7483032
• Molar Refractivity: 71.542 cm^3
• Polarizability: 27.221851 Å^3
• Polar Surface Area: 77.82 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.62
• LOG S: -3.14
• Solubility (Water): 1.79e-01 g/l

PROPERTIES

Physical Property

• Solubility: 121 mg/L; DMSO; Ethanol (hot)
• Apperance: White Solid
• Melting Point: 233-234°C
• Hydrophobicity(logP): 2.7

Safety Information

• Storage Condition: -20°C; -20°C Freezer; Room Temperature (15-30°C)
• RTECS: UV8140000
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 22; R:22
• Safety Statements: S:36/37/39
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H302
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Faceshields, Gloves

Pharmacology Properties

• Admin Routes: Oral
• Bioavailability: well-absorbed
• Excretion: Renal
• Half Life: 96 hours
• Metabolism: Hepatic
• Protein Bound: 87%
• Legal Status: Rx-only
• Pregnancy Category: B3 (Australia); C (US)
• Gene Information: human ... CYP2C9(1559), DHFRP1(573971)rat ... Dhfr(24312)

Product Information

• Purity: 97%
• Grade: VETRANAL™, analytical standard
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C12H13ClN4

DETAILS

MP Biomedicals - 02194180

Antiprotozoal compound
For Research Use Only

DrugBank - DB00205

• Drug Groups: approved
• Description: One of the folic acid antagonists that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis. [PubChem]
• Indication: For the treatment of toxoplasmosis and acute malaria; For the prevention of malaria in areas non-resistant to pyrimethamine
• Pharmacology: Pyrimethamine is an antiparasitic compound commonly used as an adjunct in the treatment of uncomplicated, chloroquine resistant, P. falciparum malaria. Pyrimethamine is a folic acid antagonist and the rationale for its therapeutic action is based on the differential requirement between host and parasite for nucleic acid precursors involved in growth. This activity is highly selective against plasmodia and Toxoplasma gondii. Pyrimethamine possesses blood schizonticidal and some tissue schizonticidal activity against malaria parasites of humans. However, the 4-amino-quinoline compounds are more effective against the erythrocytic schizonts. It does not destroy gametocytes, but arrests sporogony in the mosquito. The action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides.
• Affected Organisms: Plasmodium
• Biotransformation: Hepatic
• Absorption: Well absorbed with peak levels occurring between 2 to 6 hours following administration
• Half Life: 96 hours
• Protein Binding: 87%
• References: 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] ; 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]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S2006

Research Area: Infection
Biological Activity:
Pyrimethamine is a dihydrofolate reductase(DHFR) inhibitor with an IC50 of 15.4 nM. It is a medication used for protozoal infections. It is commonly used as an antimalarial drug (for both treatment and prevention of malaria), and is also used (combined with sulfadiazine) in the treatment of Toxoplasma gondii infections in immune-compromised patients, such as HIV-positive individuals. It interferes with folic acid synthesis by inhibiting the enzyme dihydrofolate reductase (DHFR). Folic acid is needed for DNA and RNA synthesis in many species, including protozoa. [1]

Sigma Aldrich - 46706

Legal Information
VETRANAL is a trademark of Sigma-Aldrich Co. LLC

Toronto Research Chemicals - P997240

Dihydrofolate reductase inhibitor; generally used in combination with other antimicrobial agents. Antiprotozoal (Toxoplasma); antimalarial.

REFERENCES

• 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
• 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
• http://en.wikipedia.org/wiki/Pyrimethamine
• Loutfy, M.A., et al.: Anal. Profiles Drug Subs., 12, 463 (1983)
• Leport, C., et al.: Am. J. Med., 84, 94 (1983)
• McIntosh, H.M., et al.: Ann. Trop. Med., Parasitol., 93, 265 (1983)
• Plowe, C.V., et al.: Br. Med. J., 328, 545 (1983)