Phosphoramidate protides of carbocyclic 2',3'-dideoxy-2',3'-didehydro-7-deazaadenosine with potent activity against HIV and HBV.
Synthesis of phosphoramidate protides of carbocyclic D- and L-2',3'-dideoxy-2',3'-didehydro-7-deazaadenosine 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 nucleosides against both HIV and HBV.
Gudmundsson
Kristjan S
KS
Division of Chemistry, GlaxoSmithKline, Research Triangle Park, North Carolina, USA. Kristjan.S.Gudmundsson@gsk.com
Wang
Zhicheng
Z
Daluge
Susan M
SM
Johnson
Lance C
LC
Hazen
Richard
R
Condreay
Lynn D
LD
McGuigan
Christopher
C
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; 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 / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014372:Tubercidin / Q000031:analogs & derivatives / Q000737:chemistry*
C500098:2',3'-dideoxy-2',3'-didehydro-7-deazaadenosine; D000577:Amides; D000998:Antiviral Agents; D010756:Phosphoric Acids; C011067:phosphoramidic acid; D000241:Adenosine; D014372:Tubercidin