Dihydrofolate reductase inhibitors triazines

DHFR - Dihydrofolate Reductase inhibitors - triazines, benzylpyrimidines, etc. 

Chloroguanide hydrochloride (Paludrine) is activated to a triazine metabolite, cycloguanil, which also interferes with parasite folic acid synthesis. It is a dihydrofolate reductase inhibitor that is used for the prophylaxis of malaria caused by all susceptible strains of plasmodia. Chloroguanide is rapidly absorbed from the gas-... 

Fig. 7.15 The variation in torsion angles can be effectively represented as a series of dials, where the time corresponds to the distance from the centre of the dial. Data from a molecular dynamics simulation of an intermolecular complex between the enzyme dihydrofolate reductase and a triazine inhibitor [Leach and Klein 1995].

The role of drug-membrane interactions in overcoming, or at least in reducing, resistance will be discussed using two examples of antibacterials. A series of 5-(substituted) benzyl-2,4-diaminopyrimidines and 4,6-diamino-l,2-dihydro-2,2-dimethyl-l-(3-substituted)phenyl-s-triazines, inhibitors of dihydrofolate reductase (DHFR), were tested against sensitive and resistant E. coli cell cultures as well as against E. coli-derived DHFR [55] and compared with the effect on sensitive and resistant murine tu-... 

A number of compounds derived from biguanides, triazines and diami-nopyrimidines have been shown to be potent inhibitors of dihydrofolate reductase (DHFR) and, therefore, occupy an important position in the chemotherapy of human malaria and bacterial infections. 

The traditional one-pot , three-component synthesis was adapted successfully for combinatorial mixture synthesis of dihydrophenyl triazines, which are nonclassical, dihydrofolate reductase (DHFR) inhibitors. The products precipitated out of the reaction mixture and could be collected easily and cleansed by washing. The reactions were monitored by TLC <1999BMC1255>. 

A Molecular Shape Analysis and Quantitative Structure-Activity Relationship Investigation of Some Triazine-Antifiilate Inhibitors of Leishmania major Dihydrofolate Reductase. 

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