New Dinucleoside Phosphonate Derivatives as Prodrugs of 3′-Azido-3′-Deoxythymidine and β-L-2′,3′-Dideoxy-3′-Thiacytidine: Synthesis and Anti-HIV Properties

Abstract

New phosphonate homodimers of 3′-azido-3′-deoxythymidine (AZT) and a phosphonate heterodimer of β-L-2′,3′-dideoxy-3′-thiacytidine (3TC) and AZT were synthesized. The compounds demonstrated moderate anti-HIV activity. Stability of the compounds in human blood serum was studied. A correlation between anti-HIV activity and stability was defined.

Keywords:

• Antiviral nucleosides
• HIV nucleosides
• nucleoside phosphonates
• modified nucleosides

ABBREVIATIONS

HIV-1	=	human immunodeficiency virus type 1
AZT	=	3′-azido-3′-deoxythymidine
3TC	=	β-L-2′,3′-dideoxy-3′-thiacytidine
FLT	=	3′-fluoro-3′-deoxythymidine
PMPA	=	9-[2-(R)-(phosphonomethoxy)propyl]adenine
DCC	=	N,N′-dicyclohexylcarbodiimide
TPS-Cl	=	2,4,6-triisopropylbenzenesulfonyl chloride.