SYNTHESIS AND ANTIVIRAL ACTIVITY OF ACYCLIC NUCLEOTIDE ANALOGS DERIVED FROM 6-(AMINOMETHYL)PURINES AND PURINE-6-CARBOXAMIDINES

The synthesis of a series of 9-(2-phosphonomethoxyalkyl) derivatives o f 6-(aminomethyl)purine 11, 2-amino-6-(aminomethyl)purine 12 and purin e-6-carboxamidine 14 is reported. The 6-cyanopurines 1 and 2 were sele ctively alkylated with 2-[bis(isopropyloxy)phosphonylmethoxy]alkyl syn thons 3 and 4 at the 9-position. Catalytic hydrogenation of the obtain ed opropyloxy)phosphonylmethoxy]alkyl}-6-cyanopurines 9 and 10 followe d by treatment with bromotrimethylsilane afforded the title compounds 11 and 12. Analogous acyclic nucleotides derived from purine-6-carboxa midines 14 were prepared from the cyanopurines 9a and 10a by treatment with sodium methoxide and ammonium chloride followed by deprotection. Compounds 11 and 12 exhibited moderate activity (MIC(50) = 3-50 mu g/ ml) against herpes simplex virus type 1, varicella-zoster virus and Mo loney murine sarcoma virus in vitro.