SYNTHESIS OF 2'-AMINOMETHYL DERIVATIVES OF N-(2-(PHOSPHONOMETHOXY)ETHYL) NUCLEOTIDE ANALOGS AS POTENTIAL ANTIVIRAL AGENTS

A series of purine and pyrimidine N-(2-(phosphonomethoxy)ethyl) deriva tives bearing aminomethyl, (dimethylamino)methyl, morpholinomethyl, an d (trimethylammonio)methyl groups at the 2'-position were synthesized. The compounds were prepared by alkylation of the heterocyclic bases w ith appropriately substituted (aminoalkyl)oxiranes followed by condens ation of the resulting intermediates with dialkyl ((p-tolylsulfonyl)ox y)methanephosphonate and subsequent treatment of the obtained diester with bromotrimethylsilane. 9-(3-Amino-2(phosphonomethoxy)propyl)adenin e (2a) proved active against varicella tester virus (VZV), cytomegalov irus (CMV), and Moloney murine sarcoma virus (MSV) in the concentratio n range of 7-35 mu g/mL. None of the other aminoalkyl derivatives demo nstrated significant antiviral activity against herpes simplex virus t ype 1 and 2 (HSV-1 and HSV-2), VZV, (CMV), vaccinia virus (VV), MSV, a nd human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2).