Synthesis and biological activity of nucleosides and nucleotides related to the antitumor agent 2-beta-D-ribofuranosylthiazole-4-carboxamide.
Phosphorylation of 2-beta-D-ribofuranosylthiazole-4-carboxamide (1) provided the 5'-phosphate 2, which was converted to the corresponding 5'-triphosphate 4 and the cyclic 3',5'-phosphate 5. Treatment of 2-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)thiazole-4-carbonitrile (6) with NH3-NH4Cl provided 2-beta-D-ribofuranosylthiazole-4-carboxamidine hydrochloride (7), and treatment with H2S-pyridine provided the corresponding 4-thiocarboxamide 9. Compound 9 was treated with ethyl bromopyruvate, followed by treatment with methanolic ammonia, to yield 2'-(2-beta-D-ribofuranosylthiazol-4-yl)thiazole-4'-carboxamide (11). 5'-Phosphate 2 was cytotoxic to L1210 cells in culture and significantly effective against the intraperitoneally implanted murine leukemias in mice. Amidine 7 was slightly toxic to L1210 in culture and inhibitory to purine nucleoside phosphorolysis. The cyclic 3',5'-phosphate 5 was less effective than the corresponding 5'-phosphate 2 or the parent nucleoside 1 as an antitumor agent.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D007939:Leukemia L1210 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010766:Phosphorylation; D012254:Ribavirin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000627:therapeutic use; D012263:Ribonucleosides / Q000138:chemical synthesis*
D000970:Antineoplastic Agents; D012263:Ribonucleosides; D012254:Ribavirin; C033706:tiazofurin