- 2-Substituted-4-substituted-1,3-dioxolanes and use thereof
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Nucleoside analogues containing a 1,3-dioxolane structure are suitable antiviral agents, particulary for the treatment of the HIV infections in mammals, especially humans. Examples of the nucleoside analogues include: cis-2-acetoxymethyl-4-(thymin-1′-yl)-1,3,-dioxolane, cis-2-hydroxymethyl-4-(thymin-1′-yl)-1,3-dioxolane, cis-2-benzoyloxymethyl-4-(cytosin-1′-yl)-1,3-dioxolane, and cis-2-hydroxymethyl-4-(cytosin-1′-yl)-1,3-dioxolane. These compounds can be in the form of their racemates or their separate enantiomers.
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Page column 51 -52
(2010/11/29)
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- Enantiomerically pure β-D-dioxolane-nucleosides
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A method and composition for the treatment of humans infected with HIV that includes the administration of an HIV treatment amount of an enantiomerically pure β-D-dioxolanyl purine nucleoside of the formula: STR1 wherein R is OH, Cl, NH2, or H,
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- Process for the preparation of enantiomerically pure β-D-(-)-dioxolane-nucleosides
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An asymmetric process for the preparation of enantiomerically pure β-D-(-)-dioxolane-nucleosides. The enantiomerically pure dioxolane nucleosides are active HIV agents, that are significantly more effective than the prior prepared racemic mixtures of the
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- Divergent Asymmetric Syntheses of Dioxolane Nucleoside Analogues
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Oxidative degradation of benzyloxymethylacetals derived from D-mannitol or L-ascorbic acid provides dioxolane intermediate 6 and 7 useful in the synthesis of all the stereoisomers of dioxolane nucleoside analogues.
- Evans, Colleen A.,Dixit, Dilip M.,Siddiqui, M. Arshad,Jin, Haolun,Tse, H. L. Allan,et al.
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p. 2319 - 2322
(2007/10/02)
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- Asymmetric Synthesis of 1,3-Dioxolane-Pyrimidine Nucleosides and Their Anti-HIV Activity
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In order to study the structure-activity relationships of dioxolane nucleosides as potential anti-HIV agents, various enantiomerically pure dioxolane-pyrimidine nucleosides have been synthesized and evaluated against HIV-1 in human peripheral blood mononuclear cells.The enantiomerically pure key intermediate 8 has been synthesized in nine steps from 1,6-anhydro-D-mannose (1), which was condensed with 5-substituted pyrimidines to obtain various dioxolane-pyrimidine nucleosides.Upon evaluation of these compounds, cytosine derivative 19 was found to exhibit the most potent anti-HIV agent although it is the most toxic.The order of anti-HIV potency was as follows: cytosine (β-isomer) > thymine > cytosine (α-isomer) > 5-chlorouracil > 5-bromouracil > 5-fluorouracil derivatives.Uracil, 5-methylcytosine, and 5-iodouracil derivatives were found to be inactive.Interestingly, α-isomer 20 showed good anti-HIV activity without cytotoxicity.As expected, other α-isomers did not exhibit any significant antiviral activity. (-)-Dioxolane-T was 5-fold less effective against AZT-resistant virus than AZT-sensitive virus.
- Kim, Hea O.,Ahn, Soon K.,Alves, Antonio J.,Beach, J. Warren,Jeong, Lak S.,et al
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p. 1987 - 1995
(2007/10/02)
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- Asymmetric synthesis of enantiomerically pure (-)-(1'R,4'R)-dioxolane-thymine and its anti-HIV activity
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An asymmetric synthesis leading to the enantiomerically pure dioxolane-T has been achieved and its crystal structure has been determined and compared to the previously reported racemate. (-)-(1'R,4'R)-dioxolane-T was found to have potent and selective ant
- Chu,Ahn,Kim,Beach,Alves,Jeong,Islam,Van Roey,Schinazi
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p. 3791 - 3794
(2007/10/02)
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- (±)-Dioxolane-T ((±)-1-[(2β,4β)-2-(hydroxymethyl)-4-dioxolanyl]thymine). A new 2',3'-dideoxynucleoside prototype with in vitro activity against HIV
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A novel analogue of 3'-deoxythymidine, in which the 3'-carbon is replaced by oxygen, was synthesized in 5 steps from benzyloxyacetaldehyde dimethyl acetal and (±)-methyl glycerate. In ATH8 cells, this analogue showed significant inhibition of the infectiv
- Norbeck,Spanton,Broder,Mitsuya
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p. 6263 - 6266
(2007/10/02)
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