1-Amino-3-(1<i>H</i>-1,2,3-triazol-1-yl)propylphosphonates as Acyclic Analogs of Nucleotides
作者:Iwona E. Głowacka、Jan Balzarini、Dorota G. Piotrowska
DOI:10.1002/ardp.201300471
日期:2014.7
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)
从对映体纯的 (R)- 和 (S)- 获得了一系列新的 1-氨基-3-(1H-1,2,3-三唑-1-基) 丙基膦酸酯 (R)- 和 (S)-16 1-叔丁氧基羰基 (Boc)-氨基-3-叠氮基丙基膦酸酯和 N-炔丙基化核碱基,产率良好。评估了所有 1,2,3-三唑基膦酸酯 (R)- 和 (S)-16 对多种 DNA 和 RNA 病毒的活性。化合物 (R)-16g(B = 3-乙酰吲哚)在 HeLa 细胞培养物中对水泡性口炎病毒具有中等活性(EC50 = 45 µM)。此外,(S)-16c (B = 腺嘌呤)、(R)-16f (B = N3-Bz-benzuracil)、(R)-16g (B = 3-乙酰吲哚) 和 (R)-16h (B = 5,6-二甲基苯并咪唑)对 Crandell-Rees 猫肾 (CRFK) 细胞具有细胞毒性(CC50 分别为 2.9、45、72 和 96 µM)。化合物