title: Synthesis of novel 2'-fluoro-3'-hydroxymethyl-5'-deoxythreosyl phosphonic acid nucleoside analogues as antiviral agents.
abstract: A series of purine 5'-deoxyphosphonate analogues were designed and synthesized to mimic naturally occurring purine monophosphate from 1,3-dihydroxyacetone as starting material. The discovery of threosyl phosphonate nucleoside (PMDTA, EC50 = 2.53 μM) as a potent anti-HIV agent has led to the synthesis and biological evaluation of 2',3'-modified 5'-deoxyversions of the threosyl phosphonate nucleosides. The synthesized 2'-fluoro-3'-hydroxymethyl 5'-deoxythreosyl phosphonic acid nucleoside analogues 14, 18, 23, and 27 were tested for anti-HIV activity as well as cytotoxicity. The adenine analogue 18 exhibits weak in vitro anti-HIV-1 activity (EC50 = 19.2 μM).
authors.affiliation: a BK-21 Project Team, College of Pharmacy Chosun University , Kwangju , Republic of Korea.
authors.forename: Kyung Mi
authors.initials: KM
authors.lastname: Kim
authors.forename: Joon Hee
authors.initials: JH
authors.lastname: Hong
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D010757:Phosphorous Acids / Q000737:chemistry*
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D009705:Nucleosides; D010757:Phosphorous Acids; C570063:phosphonic acid