NOVEL NON-CLASSICAL FOLATE ANALOGUE INHIBITORS OF GLYCINAMIDE RIBONUCLEOTIDE FORMYLTRANSFERASE (GARFT)

摘要

Several new 10-formyl and 10-hydroxymethyl derivatives of 5,8,10-trideazapteroic acid are provided, as well as procedures for their preparation. These compounds were shown to be powerful inhibitors of glycinamide ribonucleotide formyltransferase (GARFT), an enzyme that mediates the de novo biosynthesis of purine nucleotides that are required for DNA synthesis and cell division. Due to their ability to interfere with nucleotide biosynthesis and to penetrate microbial cells they are anti-microbial agents and are useful for the treatment of Pneumocystis carinii infection in AIDS and other infections responding to folate based antimicrobial agents.