Synthesis and Antiviral Evaluation of 3′‐Fluoro‐4′‐modified‐5′‐norcarbocyclic Nucleoside Phosphonates. (31st January 2019)

• Record Type: Journal Article
• Authors: Geant, Pierre‐Yves; Kaci, Malika; Uttaro, Jean‐Pierre; Périgaud, Christian; Mathé, Christophe
• Is Part Of: ChemMedChem. Volume 14:Number 5(2019)
• Page Start: 522
• Page End: 526
• Publication Date: 2019-01-31
• Subjects: 3′-fluoro-5′-norcarbocyclic nucleosides -- anti-HIV -- antiviral agents -- phosphonates; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201800804
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: The synthesis and anti‐HIV evaluation of hitherto unknown 3′‐fluoro‐5′‐norcarbocyclic nucleoside phosphonates bearing adenine with modifications at the 4′ position (ethynyl, vinyl, ethyl, hydroxymethyl) is described. One of the synthesized compounds was found to be an inhibitor of HIV‐1 replication, but with moderate efficiency relative to ( R )‐9‐(2‐phosphonylmethoxypropyl)adenine (( R )‐PMPA, tenofovir), with no concomitant cytotoxicity. Abstract : Nucleoside phosphonates against HIV : The racemic synthesis of 3′‐fluoro‐4′‐modified‐5′‐norcarbocyclic nucleoside phosphonates with adenine as a nucleobase was undertaken, and the resulting compounds were evaluated for anti‐HIV activity. The 3′‐fluoro‐4′‐vinyl‐5′‐norcarbocyclic nucleoside phosphonate (±)‐9 exhibited anti‐HIV‐1 activity, but with lower efficiency than ( R )‐PMPA (tenofovir) without concomitant cytotoxicity, whereas the introduction of 4′‐substituents such as ethynyl, ethyl, or hydroxymethyl resulted in loss of activity.