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Folate antagonists. 17 . Synthesis and biological properties of a 2,4‐diamino‐6‐thioquinazoline analog of aminopterin
Author(s) -
Werbel Leslie M.,
Newton Linda,
Elslager Edward F.
Publication year - 1980
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.5570170315
Subject(s) - aminopterin , chemistry , plasmodium berghei , dihydrofolate reductase , folic acid , folic acid antagonists , biochemistry , pharmacology , stereochemistry , methotrexate , enzyme , immunology , malaria , medicine , biology
A multistep route for the synthesis of N ‐[4‐[(2,4‐diamino‐6‐quinazolinyl)thio]benzoyl]‐L‐glutamic acid (2) from 4‐mercaptobenzoic acid and 5‐chloro‐2‐nitrobenzonitrile is described. Although this aminopterin analog lacked significant antimalarial activity, it was a potent inhibitor of dihydrofolate reductase from Trypanosoma cruzi. The pteroic ester analog 11 , however, was active against Plasmodium berghei infections in mice at high doses.