Synthesis and antitumor activity of 2-beta-D-ribofuranosylselenazole-4- carboxamide and related derivatives.
Treatment of 2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl-1-carbonitrile with hydrogen selenide provided 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonselenoamide (3). Compound 3 was treated with ethyl bromopyruvate to provide ethyl 2-(2,3,5-tri-O-benzoyl-D-ribofuranosyl)selenazole-4-carboxylates, which after ammonolysis were converted to 2-beta-D-ribofuranosylselenazole-4-carboxamide (6) and its alpha-analogue 7, respectively. Acetylation of nucleoside 6 provided 2-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)selenazole-4-carboxamide, and phosphorylation of 6 provided the corresponding 5'-phosphate 9. Compounds 6 and 9 were found to be cytotoxic toward P388 and L1210 cells in culture and effective against Lewis lung carcinoma in mice.
D000818:Animals; D000970:Antineoplastic Agents; D055598:Chemical Phenomena; D002621:Chemistry; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000627:therapeutic use; D012643:Selenium
D000970:Antineoplastic Agents; D012263:Ribonucleosides; D012643:Selenium