Pyrimethamine

Base Information

• Chemical Name: Pyrimethamine
• CAS No.: 58-14-0
• Molecular Formula: C12H13ClN4
• Molecular Weight: 248.715
• Hs Code.: 29335990
• European Community (EC) Number: 200-364-2
• NSC Number: 757306,3061
• UN Number: 2811
• UNII: Z3614QOX8W
• DSSTox Substance ID: DTXSID9021217
• Nikkaji Number: J4.589F
• Wikipedia: Pyrimethamine
• Wikidata: Q421072
• NCI Thesaurus Code: C788
• RXCUI: 9010
• Pharos Ligand ID: G5NUG5N82974
• Metabolomics Workbench ID: 42609
• ChEMBL ID: CHEMBL36
• Mol file: 58-14-0.mol

Synonyms:Chloridin;Daraprim;Malocide;Pyrimethamine;Tindurine

Chemical Property of Pyrimethamine

Chemical Property:

• Appearance/Colour: white solid
• Vapor Pressure: 8.34E-10mmHg at 25°C
• Melting Point: 233-234°C
• Refractive Index: 1.655
• Boiling Point: 491.5 °C at 760 mmHg
• PKA: pKa 7(t=20.0) (Uncertain)
• Flash Point: 251 °C
• PSA: 77.82000
• Density: 1.305 g/cm³
• LogP: 3.68620
• Storage Temp.: 0-6°C
• Solubility.: Prepare the solution immediately before use. Dissolve 0.25 g in a mixture of 1 volume of methanol R and 3 volumes of methylene chloride R and dilute to 10 mL with the same mixture of solvents. The solution is clear (2.2.1) and not more intensely coloured than reference solution BY6 (2.2.2, Method II).
• Water Solubility.: <0.01 g/100 mL at 21℃
• XLogP3: 2.7
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 2
• Exact Mass: 248.0828741
• Heavy Atom Count: 17
• Complexity: 243
• Transport DOT Label: Poison

Purity/Quality:

99% ^*data from raw suppliers

Pyrimethamine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 22-36
• Safety Statements: 26

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCC1=C(C(=NC(=N1)N)N)C2=CC=C(C=C2)Cl
• Recent ClinicalTrials: Pyrimethamine as an Inhibitor of NRF2 in HPV-negative Locally Advanced Head and Neck Squamous Cell Carcinoma
• Recent EU Clinical Trials: A Phase I/II Open-Label Study to Evaluate the Safety, Tolerability and Recommended Phase II Dose (RP2D) of GLG-801 in patients with Advanced Solid Tumors (Phase I); and safety, tolerability and anticancer activity of GLG-801 in patients with Metastatic TNBC (Phase II).
• Recent NIPH Clinical Trials: OPEN-LABEL, CROSSOVER EXPLORATORY STUDY TO ASSESS THE DOSE DEPENDENT EFFECT OF PYRIMETHAMINE ON EXOGENOUS AND ENDOGENOUS MATE1/2K SUBSTRATES
• General Description: Pyrimethamine is a known inhibitor of *Plasmodium falciparum* dihydrofolate reductase (PfDHFR), an enzyme critical for folate metabolism in malaria parasites, and has been used as an antimalarial agent. However, resistance has emerged due to mutations in PfDHFR, prompting the development of hybrid inhibitors like BT1, which combine structural features of pyrimethamine and flexible analogs to maintain efficacy against both wild-type and resistant strains. These advancements highlight pyrimethamine's role as a foundational scaffold in designing next-generation antimalarials to circumvent resistance.

Technology Process of Pyrimethamine

There total 29 articles about Pyrimethamine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 85.0%

2,4-diamino-5-(3-azido-4-chlorophenyl)-6-ethylpyrimidine (95458-40-5) → 2,4-diamino-5-(4-chlorophenyl)-6-ethylpyrimidine (58-14-0)

Guidance literature:

With hydrazine hydrate; for 0.25h; Heating;

DOI:10.1039/P19870002217

Reference yield: 76.0%

4-Chlorophenylboronic acid (1679-18-1) + 2,4-diamino-6-ethyl-5-iodopyrimidine (514854-13-8) → 2,4-diamino-5-(4-chlorophenyl)-6-ethylpyrimidine (58-14-0)

Guidance literature:

With dipotassium hydrogenphosphate; Pd(OAc)2(dppf)2; In 1,2-dimethoxyethane; for 24h; Heating;

Reference yield: 74.0%

5-(4-chlorophenyl)pyrimidine-2,4-diamine (17039-14-4) + Ethyl boronic acid (4433-63-0) → 2,4-diamino-5-(4-chlorophenyl)-6-ethylpyrimidine (58-14-0)

Guidance literature:

5-(4-chlorophenyl)pyrimidine-2,4-diamine; With acetic acid; trifluoroacetic acid; In acetonitrile; at 20 ℃; for 0.166667h; Green chemistry;

Ethyl boronic acid; With oxygen; In acetonitrile; at 110 ℃; for 10h; under 760.051 Torr; Green chemistry;

DOI:10.1021/acs.orglett.7b03297

upstream raw materials:

diazomethane

α-(4-chlorophenyl)-α-propionylacetonitrile

6-ethyl-2-amino-5-(4-chloro-phenyl)-3H-pyrimidine-4-thione

N-[4-ethyl-6-chloro-5-(4-chloro-phenyl)-pyrimidin-2-yl]-acetamide

Downstream raw materials:

2-amino-5-(4-chlorophenyl)-6-ethylpyrimidin-4(3H)-one

N-[2-Butyrylamino-5-(4-chloro-phenyl)-6-ethyl-pyrimidin-4-yl]-butyramide

Pentanoic acid [5-(4-chloro-phenyl)-6-ethyl-2-pentanoylamino-pyrimidin-4-yl]-amide

Diacetamidopyrimethamine

Refernces

Hybrid Inhibitors of Malarial Dihydrofolate Reductase with Dual Binding Modes That Can Forestall Resistance

10.1021/acsmedchemlett.8b00389

The research aims to develop hybrid inhibitors of Plasmodium falciparum dihydrofolate reductase (PfDHFR) that can effectively combat malaria and forestall the emergence of drug resistance in the parasite. The purpose of this study is to design and synthesize compounds that can inhibit both wild-type and multiple mutant forms of PfDHFR, which is a key enzyme in folate metabolism and a target for antimalarial drugs. The chemicals used in this process include pyrimethamine (Pyr), a known inhibitor of PfDHFR, and WR99210, a compound with flexible side chains that can avoid steric clashes with mutant PfDHFR. The researchers synthesized hybrid inhibitors BT1, BT2, and BT3, which incorporate both rigid and flexible diaminopyrimidine moieties. These compounds were tested for their inhibition constants, anti-plasmodial activities, and toxicities against mammalian cells. The results showed that BT1, in particular, had high selectivity and efficacy against both wild-type and mutant PfDHFRs, making it a promising candidate for further development as an antimalarial drug that could potentially overcome resistance issues.