136228-19-8Relevant academic research and scientific papers
Enhanced Brain Delivery of an Anti-HIV Nucleoside 2'-F-ara-ddI by Xanthine Oxidase Mediated Biotransformation
Shanmuganathan, Kirupa,Koudriakova, Tatiana,Nampalli, Satyanarayana,Du, Jinfa,Gallo, James M.,et al.
, p. 821 - 827 (2007/10/02)
In order to enhance the brain delivery of 2'-F-ara-ddI, 2'-F-ara-ddP 6 was synthesized and its in vitro and in vivo bioconversion reaction studied.For the study, a new efficient synthetic method for 2'-F-ara-ddP 6 was developed from 5-benzoyl-1,2-O-isopro
Chemistry and anti-HIV activity of 2'-β-fluoro-2',3'-dideoxyguanosine
Ford Jr.,Driscoll,Siddiqui,Kelley,Mitsuya,Shirasaka,Johns,Marquez
, p. 213 - 234 (2007/10/02)
The 2'-β-fluoro analogue of 2',3'-dideoxyguanosine has been prepared by two synthetic routes. This compound and two analogues have anti-HIV activity in at least two of three host cell systems used (ATH8, CEM, PBL). These compounds, as well as their ddGuo
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.
A more expedient approach to the synthesis of anti-HIV-active 2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl nucleosides
Wysocki Jr.,Siddiqui,Barchi Jr.,Driscoll,Marquez
, p. 1005 - 1008 (2007/10/02)
Starting with 1,3,5-tri-O-benzoyl-2-deoxy-2-fluoro-α-D-arabinofuranose, a versatile method for the synthesis of 2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl nucleosides is described and illustrated with the synthesis of 9-(2,3-dideoxy-2-fluoro-β-D-threop
