Synthesis and biological activity of 10-thia-10-deaza analogs of folic acid, pteroic acid, and related compounds.
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.
D013293:Enterococcus faecalis / Q000187:drug effects; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D005493:Folic Acid Antagonists; D007780:Lacticaseibacillus casei / Q000187:drug effects / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D011622:Pterins / Q000138:chemical synthesis* / Q000494:pharmacology; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors
D005493:Folic Acid Antagonists; D011622:Pterins; D005492:Folic Acid; D013940:Thymidylate Synthase