SYNTHESIS OF 5-(4-SUBSTITUTED BENZYL)-2,4-DIAMINOQUINAZOLINES AS INHIBITORS OF CANDIDA-ALBICANS DIHYDROFOLATE-REDUCTASE

Several 5-(4-substituted benzyl)-2,4-diaminoquinazolines were prepared as potentially selective inhibitors of Candida albicans dihydrofolate reductase. These compounds were synthesized by a novel route, which i ncluded as a key step the displacement of a fluoro group in 2,6-difluo robenzonitrile by the anions of ethyl or methyl 4-substituted phenylac etates. The resultant diarylacetates were saponified and decarboxylate d to the 2-fluoro-6-(4-substituted phenyl)benzonitriles. Ring closure of these benzonitriles with guanidine carbonate gave the 5-(4-substitu ted benzyl)-2,4-diaminoquinazolines.