Synthesis of 2,4-diamino-5-cyano-6-[[(diisopropoxyphosphoryl)methoxy]ethoxy]pyrimidine was based on the formation of the pyrimidine ring by cyclization followed by modification of the side chain by alkylation. The 5-cyano group was also transformed to a 5-formyl and 5-hydroxymethyl group by reduction. As a side product an unexpected dimer was formed. Resulting compounds were converted to the free phosphonic acids by treatment with bromotrimethylsilane followed by hydrolysis. The 5-cyano and 5-formyl derivatives showed pronounced antiretroviral activity, comparable to that of the reference drugs adefovir and tenofovir.

Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic Flemingovo nám 2 CZ 166 10 Prague 6 Czech Republic

References provided by Crossref.org

5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production

A novel type of acyclic nucleoside phosphonates derived from 2-(phosphonomethoxy)propanoic acid

An efficient microwave-assisted synthesis and biological properties of polysubstituted pyrimidinyl- and 1,3,5-triazinylphosphonic acids

Acyclic nucleoside bisphosphonates: synthesis and properties of chiral 2-amino-4,6-bis[(phosphonomethoxy)alkoxy]pyrimidines