1‐Amino‐3‐(1 H ‐1,2,3‐triazol‐1‐yl)propylphosphonates as Acyclic Analogs of Nucleotides

A new series of 1‐amino‐3‐(1 H ‐1,2,3‐triazol‐1‐yl)propylphosphonates ( R )‐ and ( S )‐ 16 were obtained from enantiomerically pure ( R )‐ and ( S )‐1‐ tert ‐butoxycarbonyl (Boc)‐amino‐3‐azidopropylphosphonates and N ‐propargylated nucleobases in good yields. All 1,2,3‐triazolylphosphonates ( R )‐ and ( S )‐ 16 were evaluated for their activities against a broad range of DNA and RNA viruses. Compound ( R )‐ 16g ( B  = 3‐acetylindole) was moderately active against vesicular stomatitis virus in HeLa cell cultures (EC 50  = 45 µM). In addition, ( S )‐ 16c ( B  = adenine), ( R )‐ 16f ( B  =  N 3 ‐Bz‐benzuracil), ( R )‐ 16g ( B  = 3‐acetylindole), and ( R )‐ 16h ( B  = 5,6‐dimethylbenzimidazole) were cytotoxic toward Crandell‐Rees feline kidney (CRFK) cells (CC 50  = 2.9, 45, 72, and 96 µM, respectively). Compounds ( R )‐ 16g , ( S )‐ 16g , and ( S )‐ 16h were slightly cytostatic to different tumor cell lines.