Phosphoramidate protides of 2',3'-dideoxy-3'-fluoroadenosine and related nucleosides with potent activity against HIV and HBV.
Syntheses of phosphoramidate protides of several 2',3'-dideoxy-3'-fluoroadenosine derivatives by treatment of the nucleoside with phosphorochloridates in the presence of pyridine and t-BuMgCl is described. Several of these protides showed significantly improved antiviral potency over the parent nucleoside against HIV and HBV. Especially marked was the improvement in potency of phosphoramidate protides of 2',3'-dideoxy-3'-fluoroadenosine against both HIV and HBV.
Gudmundsson
Kristjan S
KS
Division of Chemistry, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA. Kristjan.S.Gudmundsson@gsk.com
Daluge
Susan M
SM
Johnson
Lance C
LC
Jansen
Robert
R
Hazen
Richard
R
Condreay
Lynn D
LD
McGuigan
Christopher
C
D000577:Amides / Q000737:chemistry*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D003839:Deoxyadenosines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D016048:Dideoxyadenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D006678:HIV / Q000187:drug effects*; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000821:virology; D015394:Molecular Structure; D010756:Phosphoric Acids / Q000737:chemistry*
D000577:Amides; D000998:Antiviral Agents; D003839:Deoxyadenosines; D010756:Phosphoric Acids; D016048:Dideoxyadenosine; C062976:3'-fluoro-3'-deoxyadenosine; C011067:phosphoramidic acid