Nucleosides and nucleotides. 152. 1-(3-C-Ethynyl-β-D-ribo-pentofuranosyl)uracil as a broad spectrum antitumor nucleoside

1-(3-C- Ethynyl-β- d -ribo- pentofuranosyl)uracil (EUrd) has been designed as a potential multifunctional antitumor nucleoside antimetabolite. EUrd was synthesized by condensation of 1-O- acetyl-2,3,5-tri -O- benzoyl -3-C- ethynyl-α,β- d -ribo- pentofuranose (6) and bis(trimethylsilyl)uracil in the presence of trimethylsilyl triflate in CH3CN in good yield, followed by debenzoylation with NH3/MeOH. In vitro tumor cell growth inhibitory activity of EUrd against 14 human solid tumor cell lines was compared with 5-fluorouridine (FUrd), 2′-deoxy-5-fluorouridine (FdUrd), and 5-fluorouracil (5-FU) as positive controls. EUrd was a quite potent tumor cell growth inhibitor against almost all the tumor cell lines examined in this study except for human pancreas PANC-1 cells, and the potency of EUrd is about 6 to 650 times stronger than that of 5-FU and comparable to that of FUrd and FdUrd. EUrd showed also potent antitumor activity against human tumors as xenografts in nude mice when given in a daily intravenous dose of 2 mg/kg on consecutive days.