Efficient synthesis of highly active phospha-isosteres of the influenza neuraminidase inhibitor oseltamivir.
With a Hunsdiecker-Barton iododecarboxylation strategy, we converted the carboxylate group of the oseltamivir precursor into exemplary phosphonate monoesters. In all cases, K(i) values towards influenza virus sialidase remained in the sub-nanomolar range. We have thus made valuable structural space available for the design of novel oseltamivir-based tools for influenza virus research.
Carbain
Benoit
B
Department of Chemistry and Biochemistry, University of Sussex, Brighton, BN1 9QG, UK.
Collins
Patrick J
PJ
Callum
Lori
L
Martin
Stephen R
SR
Hay
Alan J
AJ
McCauley
John
J
Streicher
Hansjörg
H
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects*; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry; D053139:Oseltamivir / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*
D000998:Antiviral Agents; D063065:Organophosphonates; D053139:Oseltamivir; D009439:Neuraminidase