Synthesis and biological activity of a novel adenosine analogue, 3-beta-D-ribofuranosylthieno[2,3-d]pyrimidin-4-one.
The title nucleoside 5 was prepared by a condensation of the silylated heterocycle thieno[2,3-d]pyrimidin-4-one (1) with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (2a) in the presence of a Lewis acid or with 2,3,5-tri-O-acetyl-D-ribofuranosyl bromide (2b) in the presence of mercuric oxide and mercuric bromide. The site of ribosylation and anomeric configuration of this nucleoside were established by 1H NMR. The synthesis of 3-beta-D-ribofuranosylpyrrolo[2,3-d]pyrimidin-4-one (8), 1-phenyl-5-beta-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4-one (9), 5-methyl-3-beta-D-ribofuranosylthieno[2,3-d]pyrimidin-4-one (10), and 2-methyl-6-beta-D-ribofuranosyltriazolo[5,4-d]pyrimidin-7-one (11) is also described. The title compound inhibited the growth of murine L-1210 leukemic cells in vitro with an ID50 of 3 X 10(-5)M. The growth inhibition could not be prevented by uridine, cytidine, thymidine, deoxycytidine, cytosine, hypoxanthine, or uridine and hypoxanthine together. On the other hand, inhibition of adenosine kinase by 10(-7) M 5-iodotubercidin prevented the cytotoxic effect. Also a subline of L-1210 cells resistant to several cytotoxic adenosine analogues was also resistant to this nucleoside. Thus it appears that this compound 5 may act as an adenosine analogue.
D000241:Adenosine / Q000031:analogs & derivatives*; D000248:Adenosine Kinase / Q000032:analysis; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001711:Biotransformation; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology
D000970:Antineoplastic Agents; D011741:Pyrimidine Nucleosides; C044898:3-beta-ribofuranosylthieno(2,3-d)pyrimidin-4-one; D000248:Adenosine Kinase; D000241:Adenosine