Synthesis and testing of 5-benzyl-2,4-diaminopyrimidines as potential inhibitors of leishmanial and trypanosomal dihydrofolate reductase

Shafinaz F. Chowdhury, Ramon Hurtado Guerrero, Reto Brun, Luis M. Ruiz-Perez, Dolores Gonzalez Pacanowska, Ian H. Gilbert

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    Dihydrofolate reductase is a drug target that has not been thoroughly investigated in leishmania and trypanosomes. Work has previously shown that 5-benzyl-2,4-diaminopyrimidines are selective inhibitors of the leishmanial and trypanosome enzymes. Modelling predicted that alkyl/aryl substitution on the 6-position of the pyrimidine ring should increase enzyme activity of 5-benzyl-2,4-diaminopyrimidines as inhibitors of leishmanial and trypanosomal dihydrofolate reductase. Various compounds were prepared and evaluated against both the recombinant enzymes and the intact organisms. The presence of a substituent had a small or negative effect on activity against the enzyme or intact parasites compared to unsubstituted compounds.

    Original languageEnglish
    Pages (from-to)293-302
    Number of pages10
    JournalJournal of Enzyme Inhibition and Medicinal Chemistry
    Issue number5
    Publication statusPublished - 2002

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