Synthesis and antiviral activity of 2,4-diamino-5-cyano-6-[2-(phosphonomethoxy)ethoxy]pyrimidine and related compounds.
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.
Hocková
Dana
D
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, CZ-166 10 Prague 6, Czech Republic. lasice@uochb.cas.cz
Holý
Antonín
A
Masojídková
Milena
M
Andrei
Graciela
G
Snoeck
Robert
R
De Clercq
Erik
E
Balzarini
Jan
J
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004267:DNA Viruses / Q000187:drug effects; D006678:HIV / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
C495615:2,4-diamino-5-cyano-6-(2-(phosphonomethoxy)ethoxy)pyrimidine; D000998:Antiviral Agents; D011743:Pyrimidines; C030986:pyrimidine