5-Fluoropyrimidine nucleosides

Svirskaya PI, Yedidia V, Leznoff CC, Miller JM (1985) Huorinated heterocychc compounds. 2. 2,4-difluoro and 4-amino-2-fluoropyrimidines, nucleoside base analogs. J Heterocycl Chem 22 149-153... 

Lang, T.T., Seiner, M., Young, J.D., and Cass, C.E. (2001) Acquisition of human concentrative nucleoside transporter 2 (hcnt2) activity by gene transfer confers sensitivity to fluoropyrimidine nucleosides in drug-resistant leukemia cells. Molecular Pharmacology, 60 (5), 1143-1152. 

Fluoriuation (5, 153 154). The very unstable and reactive 2, 3, 5 -tris-0- cetyl-8-fluoroadenosine (2) has been prepared for the first time by reaction of (1) with KF in the presence of 18-crown-6 with acetonitrile as solvent yield 257.. The product is of interest since 5-fluoropyrimidine nucleosides have nti-tumor activity. 

Cook AF, Holman MJ, Kramer MJ, Trown PW (1979) Fluorinated pyrimidine nucleosides. 3. Synthesis and antitumor activity of a series of 5 -deoxy-5-fluoropyrimidine nucleosides. JMed Chem 22 1330-1335... 

The DNA-mediated effects of fluropyrimidines can be modulated by a number of agents, such as leucovorin (LV), levamisole, and interferon-alpha (IFN-alpha). LV prolongs TS inhibition by increasing the availability of the reduced folate cofactor necessary for formation of the inactive TS-FdUMP complex (21) (Fig. 4). Studies show alpha-interferon can potentiate 5-FU-mediated cyotoxicity, but the mechanisms are not yet defined (22,23). Another approach to modulate the activity of fluoropyrimidines is the use of the nucleoside transport inhibitor dipyridamole. Dipyridamole probably permits... 

Nucleosides Derived from Fluorinated Bases Many nucleosides have been synthesized from different fluoropyrimidines (uracil, thymidine, cytosine) or fluoropurine (adenine, guanine) bases, which are generally prepared by electro-... 

Greenberg, N., Schumm, D.E., and Wehh, T.E. (1977) Uridine kinase activities and pyrimidine nucleoside phosphorylation in fluoropyrimidine-sensitive and -resistant cell lines of the Novikoff hepatoma. The Biochemical Journal, 164 (2), 379-387. 

The pyrimidine antimetabolites encompass a diverse group of drugs that inhibit RNA and DNA function in a variety of ways. Some, such as the fluoropyrimidines and the purine base analogs (6-mercaptopurine and 6-thioguanine) inhibit the synthesis of essential precursors of DNA. Others, particularly the cytidine and adenosine nucleoside analogs, become incorporated into DNA and block its further elongation and its function. Other metabohc effects of these analogs may contribute to their cytotoxicity and even them ability to induce differentiation. 

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