Premium
Monocyclic pteridine analogues. A pyrazine analogue of methotrexate
Author(s) -
Lever O. William,
Vestal B. Randall
Publication year - 1985
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.5570220102
Subject(s) - chemistry , pteridine , pyrazine , methotrexate , deoxygenation , dihydrofolate reductase , stereochemistry , hydrolysis , condensation , pyrimidine , medicinal chemistry , organic chemistry , enzyme , immunology , catalysis , physics , thermodynamics , biology
Reaction of aminocyanoacetamide with bromomethylpyruvaldoxime provided 3‐amino‐6‐bromomethyl‐2‐carbamoylpyrazine 4‐oxide (7) , which was converted to a pyrazine analogue (3) of methotrexate by subsequent condensation with diethyl N ‐[4‐(methylamino)benzoyl]‐L‐glutamate, deoxygenation, and hydrolysis. The methotrexate analogue 3 was a poor inhibitor (I 50 > 150 μM) of bacterial or mammalian dihydrofolate reductase.