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Synthesis of 5‐(4‐substituted benzyl)‐2,4‐diaminoquinazolines as inhibitors of candida albicans dihydrofolate reductase
Author(s) -
Jagdmann G. Erik,
Chan Joseph H.,
Styles Virgil L.,
Tansik Robert L.,
Boytos Christine M.,
Rudolph Sharon K.
Publication year - 1995
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570320508
Subject(s) - chemistry , dihydrofolate reductase , candida albicans , saponification , guanidine , ring (chemistry) , stereochemistry , pyrimidine , enzyme , organic chemistry , microbiology and biotechnology , biology
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 included as a key step the displacement of a fluoro group in 2,6‐difluorobenzonitrile by the anions of ethyl or methyl 4‐substituted phenylacetates. The resultant diarylacetates were saponified and decarboxylated to the 2‐fluoro‐6‐(4‐substituted phenyl)benzonitriles. Ring closure of these benzonitriles with guanidine carbonate gave the 5‐(4‐substituted benzyl)‐2,4‐diaminoquinazolines.