Collect. Czech. Chem. Commun. 1996, 61, 1525-1537

Synthesis and Antiviral Activity of Acyclic Nucleotide Analogues Derived from 6-(Aminomethyl)purines and Purine-6-carboxamidines

Michal Hoceka, Milena Masojídkováa, Antonín Holýa, Graciela Andreib, Robert Snoeckb, Jan Balzarinib and Erik De Clercqb

a Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic
b Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium


The synthesis of a series of 9-(2-phosphonomethoxyalkyl) derivatives of 6-(aminomethyl)purine 11, 2-amino-6-(aminomethyl)purine 12 and purine-6-carboxamidine 14 is reported. The 6-cyanopurines 1 and 2 were selectively alkylated with 2-[bis(isopropyloxy)phosphonylmethoxy]alkyl synthons 3 and 4 at the 9-position. Catalytic hydrogenation of the obtained 9-{2-[bis(isopropyloxy)phosphonylmethoxy]alkyl}-6-cyanopurines 9 and 10 followed by treatment with bromotrimethylsilane afforded the title compounds 11 and 12. Analogous acyclic nucleotides derived from purine-6-carboxamidines 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 (MIC50 = 3-50 μg/ml) against herpes simplex virus type 1, varicella-zoster virus and Moloney murine sarcoma virus in vitro.

Keywords: Acyclic nucleoside phosphonates; Phosphonomethoxyalkylpurine derivatives; 6-Cyanopurines; 6-(Aminomethyl)purines; Purine-6-carboxamidines; Antivirals.