6-[2-phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines: a new class of acyclic pyrimidine nucleoside phosphonates with antiviral activity.
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.
Balzarini
J
J
Rega Institute for Medical Research, K.U. Leuven, Leuven, Belgium.
Pannecouque
C
C
Naesens
L
L
Andrei
G
G
Snoeck
R
R
De Clercq
E
E
Hocková
D
D
Holý
A
A
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D019380:Anti-HIV Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D015613:Hepadnaviridae / Q000235:genetics; D006564:Herpesviridae / Q000235:genetics; D051379:Mice; D008956:Models, Chemical; D008980:Moloney murine sarcoma virus / Q000378:metabolism; D009705:Nucleosides / Q000737:chemistry; D063065:Organophosphonates / Q000737:chemistry / Q000494:pharmacology; D011212:Poxviridae / Q000235:genetics; D011741:Pyrimidine Nucleosides / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry* / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D000068698:Tenofovir
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D009705:Nucleosides; D063065:Organophosphonates; D011741:Pyrimidine Nucleosides; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; C017205:2,4-diaminopyrimidine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine