Synthesis, anti-HIV activity, and resistance profiles of ribose modified nucleoside phosphonates

  • Bioorg Med Chem Lett. 2007 Dec 15;17(24):6785-9. doi: 10.1016/j.bmcl.2007.10.038.
Richard L Mackman  1 ,  Constantine G Boojamra ,  Vidya Prasad ,  Lijun Zhang ,  Kuei-Ying Lin ,  Oleg Petrakovsky ,  Darius Babusis ,  James Chen ,  Janet Douglas ,  Deborah Grant ,  Hon C Hui ,  Choung U Kim ,  David Y Markevitch ,  Jennifer Vela ,  Adrian Ray ,  Tomas Cihlar
Affiliations
  • 1. Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA. [email protected]
PMID: 18029175 DOI: 10.1016/j.bmcl.2007.10.038
Abstract

A series of nucleoside phosphonate Reverse Transcriptase (RT) inhibitors have been synthesized and their anti-HIV activity and resistance profiles evaluated. The most potent analog [5-(6-amino-purin-9-yl)-2,5-dihydro-furan-2-yloxymethyl]-phosphonic acid (d4AP) demonstrated a HIV EC(50)=2.1 microM, and the most favorable resistance profile against HIV-1 variants with K65R, M184V or multiple Thymidine analog mutations in RT.