6‐[2‐Phosphonomethoxy)Alkoxy]‐2,4‐Diaminopyrimidines: A New Class of Acyclic Pyrimidine Nucleoside Phosphonates with Antiviral Activity

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.