Synthesis and Biological Activity of a Novel Adenosine Analogue, 3β-D-Ribofuranosylthienopyrimidin-4-one

Article abstract of DOI:10.1021/jm00382a006

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-β-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-β-D-ribofuranosylpyrrolo<2,3-d>pyrimidin-4-one (8), 1-phenyl-5-β-D-ribofuranosylpyrazolo<3,4-d>pyrimidin-4-one (9), 5-methyl-3-β-D-ribofuranosylthieno<2,3-d>pyrimidin-4-one (10), and 2-methyl-6-β-D-ribofu ranosyltriazolo<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 and ID50 of 3*10^-5 M.The growth inhibition could not be prevented bu 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