1-Amino-3-(1H-1,2,3-triazol-1-yl)propylphosphonates as acyclic analogs of nucleotides.
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.
Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Łódź, Poland.
Iwona E
IE
Głowacka
Jan
J
Balzarini
Dorota G
DG
Piotrowska
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002415:Cats; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D061565:Cycloaddition Reaction; D003588:Cytopathogenic Effect, Viral; D004267:DNA Viruses / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009711:Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012328:RNA Viruses / Q000187:drug effects; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D009711:Nucleotides; D063065:Organophosphonates; D014230:Triazoles
Antiproliferative agents; Antiviral activity; Cycloaddition; Cytotoxic activity; Triazoles