Synthesis and anti-HIV activity of 2'-fluorine modified nucleoside phosphonates: analogs of GS-9148

Richard L Mackman; Kuei-Ying Lin; Constantine G Boojamra; Hon Hui; Janet Douglas; Deborah Grant; Oleg Petrakovsky; Vidya Prasad; Adrian S Ray; Tomas Cihlar

doi:10.1016/j.bmcl.2007.11.126

Synthesis and anti-HIV activity of 2'-fluorine modified nucleoside phosphonates: analogs of GS-9148

Bioorg Med Chem Lett. 2008 Feb 1;18(3):1116-9. doi: 10.1016/j.bmcl.2007.11.126. Epub 2007 Dec 5.

Authors

Richard L Mackman¹, Kuei-Ying Lin, Constantine G Boojamra, Hon Hui, Janet Douglas, Deborah Grant, Oleg Petrakovsky, Vidya Prasad, Adrian S Ray, Tomas Cihlar

Affiliation

¹ Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA. [email protected]

PMID: 18082402
DOI: 10.1016/j.bmcl.2007.11.126

Abstract

Modified purine analogs of GS-9148 [5-(6-amino-purin-9-yl)-4-fluoro-2,5-dihydro-furan-2-yloxymethyl]-phosphonic acid (2'-Fd4AP) were synthesized and their anti-HIV potency evaluated. The antiviral activity of guanosine analog (2'-Fd4GP) was comparable that of to 2'-Fd4AP in MT-2 cells, but selectivity was reduced.

MeSH terms

Anti-HIV Agents / chemical synthesis*
Anti-HIV Agents / chemistry
Anti-HIV Agents / pharmacology*
Fluorine / chemistry*
Guanosine / analogs & derivatives*
Guanosine / chemical synthesis*
Guanosine / chemistry
Guanosine / pharmacology*
Humans
Molecular Structure
Nucleosides / chemical synthesis*
Nucleosides / chemistry
Nucleosides / pharmacology*
Organophosphonates / chemical synthesis*
Organophosphonates / chemistry
Organophosphonates / pharmacology*
Reverse Transcriptase Inhibitors / chemical synthesis*
Reverse Transcriptase Inhibitors / chemistry
Reverse Transcriptase Inhibitors / pharmacology*
Structure-Activity Relationship
Zidovudine / pharmacology

Substances

Anti-HIV Agents
Nucleosides
Organophosphonates
Reverse Transcriptase Inhibitors
Guanosine
Fluorine
Zidovudine
GS-9148