Linked Life Data

1351945

Source:http://linkedlifedata.com/resource/pubmed/id/1351945

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1992-7-27
pubmed:abstractText
The synthesis, chemistry, biochemistry, and anti-HIV activity of a series of 1-(2,3-dideoxy-2-fluoro-beta-D-threopentofuranosyl)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 compounds is a 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 greater than 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2195-201
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:1351945-Animals, pubmed-meshheading:1351945-Antiviral Agents, pubmed-meshheading:1351945-CD4-Positive T-Lymphocytes, pubmed-meshheading:1351945-Cell Line, pubmed-meshheading:1351945-Chemistry, Physical, pubmed-meshheading:1351945-Cytarabine, pubmed-meshheading:1351945-Cytidine Deaminase, pubmed-meshheading:1351945-Cytopathogenic Effect, Viral, pubmed-meshheading:1351945-Dose-Response Relationship, Drug, pubmed-meshheading:1351945-Drug Stability, pubmed-meshheading:1351945-HIV-1, pubmed-meshheading:1351945-Hydrogen-Ion Concentration, pubmed-meshheading:1351945-Macaca mulatta, pubmed-meshheading:1351945-Molecular Structure, pubmed-meshheading:1351945-Physicochemical Phenomena, pubmed-meshheading:1351945-Structure-Activity Relationship, pubmed-meshheading:1351945-Zalcitabine
pubmed:year
1992
pubmed:articleTitle
Chemistry and anti-HIV properties of 2'-fluoro-2',3'-dideoxyarabinofuranosylpyrimidines.
pubmed:affiliation
Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
pubmed:publicationType
Journal Article, Comparative Study