113512-19-9

Usage

General Description

2,4-Pyrimidinediamine, 6-ethyl-5-(4-methoxyphenyl)- is a chemical compound with the molecular formula C14H16N4O. It is a derivative of pyrimidine and contains an ethyl and 4-methoxyphenyl substituent. 2,4-Pyrimidinediamine, 6-ethyl-5-(4-methoxyphenyl)- has been studied for its potential applications as a pharmaceutical intermediate and as a building block in organic synthesis. It may also have biological activities and is of interest for research in medicinal chemistry and drug development. Additionally, it has the potential to be used in the production of various materials and compounds in the chemical industry.

Upstream product

• 113-00-8 guanidine nitrate 
• 95458-57-4 2,4-diamino-5-(3-amino-4-methoxyphenyl)-6-ethylpyrimidine 
• 50-01-1 guanidine hydrochloride 
• 21813-35-4 2,4-diamino-5-(4-chloro-3-nitrophenyl)-6-ethylpyrimidine 
• 95458-54-1 2,4-diamino-6-ethyl-5-(4-methoxy-3-nitrophenyl)pyrimidine 
• 58-14-0 2,4-diamino-5-(4-chlorophenyl)-6-ethylpyrimidine 
• 95458-55-2 2,4-diamino-5-(4-azido-3-methoxyphenyl)-6-ethylpyrimidine 
• 104-47-2 p-methoxybenzylnitrile 
• 5219-01-2 2-(4-methoxyphenyl)-3-oxopentanenitrile 

Relevant academic research and scientific papers

Pyrimethamine Derivatives: Insight into Binding Mechanism and Improved Enhancement of Mutant β- N -acetylhexosaminidase Activity

In order to identify structural features of pyrimethamine (5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine) that contribute to its inhibitory activity (IC50 value) and chaperoning efficacy toward β-N-acetylhexosaminidase, derivatives of the compound were synthesized that differ at the positions bearing the amino, ethyl, and chloro groups. Whereas the amino groups proved to be critical to its inhibitory activity, a variety of substitutions at the chloro position only increased its IC50 by 2-3-fold. Replacing the ethyl group at the 6-position with butyl or methyl groups increased IC50 more than 10-fold. Surprisingly, despite its higher IC50, a derivative lacking the chlorine atom in the para-position was found to enhance enzyme activity in live patient cells a further 25% at concentrations >100 μM, while showing less toxicity. These findings demonstrate the importance of the phenyl group in modulating the chaperoning efficacy and toxicity profile of the derivatives.

COMPOUNDS FOR THE TREATMENT OF LYSOSOMAL STORAGE DISEASES

A method of treating a lysosomal storage disease comprises administering a pyrimethamine derivative to a subject in need thereof.

Development of 2,4-diaminopyrimidines as antimalarials based on inhibition of the S108N and C59R+S108N mutants of dihydrofolate reductase from pyrimethamine resistant Plasmodium falciparum

The reduced binding of pyrimethamine to Serl08Asn (S108N) mutants of parasite dihydrofolate reductase (DHFR), which forms the basis of resistance of Plasmodium falciparum to pyrimethamine, is largely due to steric constraint imposed by the bulky side chain of N108 on Cl of the 5-p-Cl-phenyl group. This and other S108 mutants with bulky side chains all showed reduced binding to pyrimethamine and cycloguanil. Less effect on binding to some bulky mutants was observed for trimethoprim, with greater flexibility for the 5-substituent. S108N DHFR also binds poorly with other pyrimethamine derivatives with bulky groups in place of the p-Cl, and the binding was generally progressively poorer for the double (C59R+S108N) mutant. Removal of the p-Cl or replacement with m-Cl led to better binding with the mutant DHFRs. Pyrimethamine analogues with unbranched hydrophobic 6-substituents showed generally good binding with the mutant DHFRs. A number of compounds were identified with high affinities for both wild-type and mutant DHFRs, with very low to no affinity to human DHFR. Some of these compounds show good antimalarial activities against pyrimethamine-resistant P. falciparum containing the mutant DHFRs with low cytotoxicity to three mammalian cell lines.

Stuctural Studies on Bio-active Compounds. Part 5. Synthesis and Properties of 2,4-Diaminopyrimidine Dihydrofolate Reductase Inhibitors bearing Lipophilic Azido Groups

A series of 2,4-diamino-5-(azidoaryl)-6-alkylpyrimidines has been prepared.The azide (36) (MZP) can be reduced by thiol reagents to the corresponding amine (28) but reductive deazidation occured when the series of azidophenyl derivatives was heated with hydrazine hydrate.Degradation of azide (36) in a trifluoroacetic acid-trifluoromethanesulphonic acid mixture at 0 deg C affords a means of introducing the bulky trifluoromethylsulphonyloxy substituent into the hindered ortho-position of the 5-aryl substituent.The products formed from thermolysis and photolysis of the azide (36) and the planar analogue 2,4-diamino-6-azidoquinazoline (70) derive from the triplet nitrene reactive intermediates. The azido compounds are potent inhibitors of rat liver dihydrofolate reductase although not as active as metoprin.The azide (36), as its ethanesulphonic acid salt, was selected for clinical trial on the basis of its ease of synthesis and suitable biological and pharmaceutical properties, and has a shorter biological half-life than compounds of comparable hydrophobicity.