1-Amino-3-(1H-1,2,3-triazol-1-yl)propylphosphonates as acyclic analogs of nucleotides

Abstract

A new series of 1-amino-3-(1H-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 (EC50 = 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 (CC50 = 2.9, 45, 72, and 96 µM, respectively). Compounds (R)-16g, (S)-16g, and (S)-16h were slightly cytostatic to different tumor cell lines.

Keywords: Antiproliferative agents; Antiviral activity; Cycloaddition; Cytotoxic activity; Triazoles.