Synthesis and biological activity of 10-thia-10-deaza analogs of folic acid, pteroic acid, and related compounds

Abstract
The 10-thia analogs of pteroic acid, folic acid, their esters, and their 4-amino analogs were synthesized through a reaction sequence involving, as a key step, the condensation of 2-amino-3-cyano-5-chloromethylpyrazine with appropriately substituted thiols. The abilities of the products to inhibit the growth of methotrexate (MTX)-sensitive and MTX-resistant microorganisms were investigated as were their abilities to inhibit dihydrofolic acid reductase and thymidylic acid synthetase. Several compounds had high activity.

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