BIOMAT Database Logo BIOMAT Database Logo

Synthesis and anticancer evaluation of 4'-C-methyl-2'-fluoro arabino nucleosides. 2009

Kamal N Tiwari, and Anita T Shortnacy-Fowler, and William B Parker, and William R Waud, and John A Secrist
Southern Research Institute, Drug Discovery Division, Birmingham, Alabama, USA.

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.

UI MeSH Term Description Entries
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D011741 Pyrimidine Nucleosides Pyrimidines with a RIBOSE attached that can be phosphorylated to PYRIMIDINE NUCLEOTIDES. Nucleosides, Pyrimidine
D011742 Pyrimidine Nucleotides Pyrimidines with a RIBOSE and phosphate attached that can polymerize to form DNA and RNA. Nucleotides, Pyrimidine
D004354 Drug Screening Assays, Antitumor Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals. Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D001087 Arabinonucleosides Nucleosides containing arabinose as their sugar moiety. Arabinofuranosylnucleosides
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular

Related Publications

Kamal N Tiwari, and Anita T Shortnacy-Fowler, and William B Parker, and William R Waud, and John A Secrist
Design, chemical synthesis and antiviral evaluation of 2'-deoxy-2'-fluoro-2'-C-methyl-4'-thionucleosides.
April 2022, Bioorganic & medicinal chemistry letters,
Kamal N Tiwari, and Anita T Shortnacy-Fowler, and William B Parker, and William R Waud, and John A Secrist
Synthesis and characterization of 1'-C-cyano-2'-fluoro-2'-C-methyl pyrimidine nucleosides as HCV polymerase inhibitors.
March 2015, Bioorganic & medicinal chemistry letters,
Kamal N Tiwari, and Anita T Shortnacy-Fowler, and William B Parker, and William R Waud, and John A Secrist
Short synthesis and antiviral evaluation of C-fluoro-branched cyclopropyl nucleosides.
January 2007, Nucleosides, nucleotides & nucleic acids,
Kamal N Tiwari, and Anita T Shortnacy-Fowler, and William B Parker, and William R Waud, and John A Secrist
A concise synthesis of 4'-fluoro nucleosides.
November 2007, Organic letters,
Kamal N Tiwari, and Anita T Shortnacy-Fowler, and William B Parker, and William R Waud, and John A Secrist
Synthesis and antiviral activity of 2'-deoxy-2'-fluoro-2'-C-methyl purine nucleosides as inhibitors of hepatitis C virus RNA replication.
March 2006, Bioorganic & medicinal chemistry letters,
Kamal N Tiwari, and Anita T Shortnacy-Fowler, and William B Parker, and William R Waud, and John A Secrist
Nucleosides. 146. 1-Methyl-5-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil, the C-nucleoside isostere of the potent antiviral agent 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (FMAU). Studies directed toward the synthesis of 2'-deoxy-2'-substituted arabino nucleosides. 6.
December 1987, Journal of medicinal chemistry,
Kamal N Tiwari, and Anita T Shortnacy-Fowler, and William B Parker, and William R Waud, and John A Secrist
Oligodeoxynucleotides containing 2'-fluoro-arabino-nucleotide and C-nucleotide.
January 1993, Nucleic acids symposium series,
Kamal N Tiwari, and Anita T Shortnacy-Fowler, and William B Parker, and William R Waud, and John A Secrist
Synthesis and biological activities of 2'-deoxy-2'-fluoro-4'-thioarabinofuranosylpyrimidine and -purine nucleosides.
July 2000, Bioorganic & medicinal chemistry,
Kamal N Tiwari, and Anita T Shortnacy-Fowler, and William B Parker, and William R Waud, and John A Secrist
Synthesis and antiviral activity of 2'-deoxy-2'-fluoro-2'-C-methyl-7-deazapurine nucleosides, their phosphoramidate prodrugs and 5'-triphosphates.
December 2011, Bioorganic & medicinal chemistry letters,
Kamal N Tiwari, and Anita T Shortnacy-Fowler, and William B Parker, and William R Waud, and John A Secrist
Synthesis of 5'-methylene-phosphonate furanonucleoside prodrugs: application to D-2'-deoxy-2'-α-fluoro-2'-β-C-methyl nucleosides.
September 2012, Organic letters,
Copied contents to your clipboard!