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

Bioorganic & Medicinal Chemistry Letters
1996.0

Abstract

l-(3-C-Ethynyl-~-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-ct,~-D-ribo-pentofuranose (6) and bis(trimethyisilyl)uracil in the presence of Irimethylsilyl triflate in CH3CN in good yield, followed by debenzoylation with NH~/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-I 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 xenografls in nude mice when given in a dally intravenous dose of 2 mg/kg on consecutive days.

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