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Updated: Aug 20, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
6-[2-phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines: a new class of acyclic pyrimidine nucleoside phosphonates with
J Balzarini1, C Pannecouque, L Naesens
1Rega Institute for Medical Research, K.U. Leuven, Leuven, Belgium.
Abstract:
Acyclic nucleoside phosphonate derivatives containing a pyrimidine base preferably bearing amino groups at C-2 and C-4 (DAPym), and linked at the C-6 position to (S)-[3-hydroxy-2-(phosphonomethoxy)propoxy] (HPMPO), 2-(phosphonomethoxy) ethoxy (PMEO) or (R)-[2-(phosphonomethoxy)propoxy] (PMPO), display an antiviral sensitivity spectrum that closely mimic that of the parental (S)-HPMP-, PME- and (R)-PMP-purine derivatives. Several PMEO-DAPym derivatives proved as potent as PMEA (adefovir) and (R)-PMPA (tenofovir) in inhibiting Moloney murine sarcoma virus (MSV)-induced tumor formation in newborn NMRI mice. The HPMPO-, PMEO- and PMPO-DAPym derivatives represent a novel well-defined subclass among the acyclic nucleoside phosphonates endowed with potent and selective antiviral activity.
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