124424-25-5Relevant academic research and scientific papers
2'-fluorofuranosyl derivatives and novel method of preparing 2'-fluoropyrimidine and 2'-fluoropurine nucleosides
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, (2008/06/13)
A compound has the formula STR1 wherein R is selected from the group consisting of (C7 -C20)aroyl, (C6 -C20)aryl, aralkyl and alkylaryl, and (C1 -C10)alkyl-di(C6 -C20)aryl Si, R' is selected from the group consisting of (C1 -C10)alkyl, (C7 -C20)aroyl and (C2 -C12)acyl, all of which may be further substituted with O, S, N or alkyl, and R'" is selected from the group consisting of halogen, (C1 -C10)alkoxy, (C1 -C10)acyloxy, O-methane-sulfonyl and O-p-toluenesulfonyl. A composition of matter comprises 0.001 to 99.999 wt % of the above compound.
Chemistry and anti-HIV properties of 2'-fluoro-2',3'- dideoxyarabinofuranosylpyrimidines
Siddiqui,Driscoll,Marquez,Roth,Shirasaka,Mitsuya,Barchi Jr.,Kelley
, p. 2195 - 2201 (2007/10/02)
The synthesis, chemistry, biochemistry, and anti-HIV activity of a series of 1-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl)pyrimidines have been studied in an attempt to find useful anti-AIDS drugs. Synthesis is carried out via a 2,3-dideoxyribose intermediate which facilitates the preparation of analogues by removing the sugar 3'-hydroxyl group prior to, rather than after, condensation with a uracil or cytosine aglycon. The 2'-F-dd-uridine analogues 7a-d (with H, F, Cl, and CH3 substitution in the 5-position) as well as the 4-deoxy compound (12b) are nonprotective to ATH8 or CEM cells infected with HIV-1. In the corresponding cytidine series, the 5-chloro analogue (11) is inactive. However, 2'-fluoro-2',3'- dideoxyarabinosylcytosine, 10a, and its 5-fluoro analogue, 10b, are both active. While neither compound is as potent as ddC or 5-F-ddC (2b), 10b gives complete protection against the cytopathic effects of HIV in both host cell lines. 2'-Fluoro substitution confers increased chemical and enzymatic stability on dideoxynucleosides. Even though dideoxy pyrimidine nucleosides are inherently more stable than the corresponding purine analogues toward acid-catalyzed cleavage of the glycosidic bond, 2'-fluoro substitution (10a) still increases stabilization relative to ddC (2b). No detectable deamination by partially purified cytidine deaminase is observed with the 2'-fluoro compounds 10a, 10b, or 11 under conditions which rapidly deaminate cytidine. A small amount of 2'-F-dd-ara-U (7a) is formed from 10a in monkey plasma after >24 h of exposure. The octanol-water partition coefficients for the dideoxynucleosides in this study indicate their hydrophilic character, with log P values varying from -0.28 to -1.18.
Synthesis and antiviral activity of monofluoro and difluoro analogues of pyrimidine deoxyribonucleosides against human immunodeficiency virus (HIV-1)
Martin,Bushnell,Duncan,Dunsdon,Hall,Machin,Merrett,Parkes,Roberts,Thomas,Galpin,Kinchington
, p. 2137 - 2145 (2007/10/02)
A range of 2'-fluoro and 2',3'-difluoro analogues of pyrimidine deoxyribonucleosides have been synthesized and evaluaed against human immunodeficiency virus (HIV-1) in a human lymphoblastoid cell line. Among these compounds, 1-(2,3-dideoxy-2-fluoro-β-D-threopentofuranosyl)cytosine (12), 2',3'-didehydro-2',3'-dideoxy-2'-fluorocytidine (35), 1-(2,3-dideoxy-2,3-difluoro-β-D-arabinofuranosyl)cytosine (41), and 3'-deoxy-2',3'-didehydro-2'-fluorothymidine (45) were found to have significant antiviral activity, with IC50 values of 0.65, 10, 10, and 100 μM, respectively. The structure-activity relationships are discussed.
Synthesis and anti-HIV activity of several 2'-fluoro-containing pyrimidine nucleosides
Sterzycki,Ghazzouli,Brankovan,Martin,Mansuri
, p. 2150 - 2157 (2007/10/02)
Several 2'-fluoroarabino-2',3'-dideoxy- and 2'-fluoro-2',3'-unsaturated 2',3'-dideoxy pyrimidine nucleoside analogues are reported. The saturated analogues 1-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl)thymine (2'-threo-FddT, 33), 1-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl)uracil (2'-threo-FddU, 22) were readily prepared from the corresponding 2'-deoxy-2'-fluoroarabinosyl nucleoside analogue by radical deoxygenation of the 3'-OH. The unsaturated compounds 1-(2,3-dideoxy-2-fluoro-β-D-glycero-pent-2-enofuranosyl)thymine (2'-Fd4T, 40) and 1-[5-O-(monomethoxytrityl)-2-fluoro-2,3-dideoxy-β-D-glycero -pent-2-enofuranosyl]uracil (39) were synthesized by an elimination reaction of the O-2,3'-anhydro-2'-fluoro-lyxo derivatives under basic conditions. The cytidine analogues 28 and 41 were prepared by amination of the corresponding uridine derivatives; compounds 28 and 41 were deprotected to give 1-(2,3-dideoxy-2-fluoro-β-D-arabinofuranosyl)cytidine (2'-threo-FddC, 29) and 1-(2,3-dideoxy-2-fluoro-β-D-glycero-pent-2-enofuranosyl)cytosine (2'-Fd4C, 42), respectively. All of these novel compounds were evaluated in vitro against human immunodeficiency virus (HIV) (LAV isolate). 2'-threo-FddC (29) was the most active of the newly synthesized substances against HIV with an ID50 of 0.8 μg/mL; ddC had an ID50 of 0.007 μg/mL. Because of its potency in the initial tests, 29 was further evaluated in both T cells and macrophage/monocyte cell lines, with several different isolates of HIV. Although 2'-threo-FddC (29) exhibited good antiviral activity in these systems, it was less active than AZT in these assays. At 1 μM the inhibition of CFU-GM by 29 was found to be 35-40%; this is slightly higher than seen with AZT.
