Synthesis and anticancer evaluation of 4'-C-methyl-2'-fluoro arabino nucleosides.
As part of an ongoing program to develop novel antitumor agents over the years, we have synthesized and evaluated a number of 4'-C-substituted nucleosides. A few years ago, we reported the first synthesis of 4'-C-hydroxymethyl-2'-fluoro arabino nucleosides, which did not exhibit any cytotoxicity. In our exploration of related compounds, we synthesized and evaluated the 4'-C-methyl-2'-fluoro arabino nucleosides in both the purine and pyrimidine series. In the pyrimidine series, 1-(4-C-methyl-2-fluoro-beta-D-arabinofuranosyl) cytosine (13) was found to be highly cytotoxic and had significant antitumor activity in mice implanted with human tumor xenografts. The synthesis and anticancer activity of this series of nucleosides are reported.
Tiwari
Kamal N
KN
Southern Research Institute, Drug Discovery Division, Birmingham, Alabama, USA.
Shortnacy-Fowler
Anita T
AT
Parker
William B
WB
Waud
William R
WR
Secrist
John A
JA
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D054879:Halogenation; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D011742:Pyrimidine Nucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D011741:Pyrimidine Nucleosides; D011742:Pyrimidine Nucleotides