1-<3-deoxy-3-C-(hydroxymethyl)-β-D-arabino-pentofuranosyl>thymine | 130351-55-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-<3-deoxy-3-C-(hydroxymethyl)-β-D-arabino-pentofuranosyl>thymine
• 英文别名: 1-<3-C-(hydroxymethyl)-3-deoxy-β-D-threo-pentofuranosyl>thymine；2,4(1H,3H)-Pyrimidinedione, 1-(3-deoxy-3-(hydroxymethyl)-beta-D-arabinofuranosyl)-5-methyl-；1-[(2R,3S,4S,5S)-3-hydroxy-4,5-bis(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 130351-55-2
• 化学式: C₁₁H₁₆N₂O₆
• 分子量: 272.258
• InChiKey: SAQLIIXINWYWJX-BDNRQGISSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  119
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  胸腺嘧啶 在 palladium on activated charcoal 吡啶 、 sodium hydroxide 、 C₄F₉SO₃K 、 氨 、 氢气 、 六甲基二硅氮烷 作用下， 以 甲醇 、 乙醇 、 乙腈 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 191.0h， 生成 1-<3-deoxy-3-C-(hydroxymethyl)-β-D-arabino-pentofuranosyl>thymine
  参考文献：
  名称：

  Syntheses and biological evaluations of 3'-deoxy-3'-C-branched-chain-substituted nucleosides

  摘要：

  Various 3'-deoxy-3'-C-(hydroxymethyl)-, 3'-deoxy-3'-C-(fluoromethyl)-, 3'-deoxy-3'-C-(azidomethyl)-, and 3'-deoxy-3'-C-(aminomethyl)-substituted nucleosides (total 12 compounds) have been synthesized and evaluated against L1210, P388, S-180, and CCRF-CEM cells and HSV-1, HSV-2, and HIV-1 in culture. Only 3'-deoxy-3'-C-(hydroxymethyl)thymidine (36) was found to show significant anticancer activity against L1210, P388, S-180, and CCRF-CEM cells with ED50 values of 50, 5, 10, and 1 muM, respectively. None of these compounds demonstrated significant antiviral activity against HSV-1, HSV-2, or HIV-1. These compounds were also evaluated against thymidine kinases derived from HSV-1 (strain KOS), HSV-2 (strain 333), and mammalian (K562) cells. The thymidine kinase (HSV-1 strain KOS) was inhibited significantly by both 3'-deoxy-3'-C-(hydroxymethyl)- and 3'-deoxy-3'-C-(fluoromethyl)thymidine.

  DOI：

  10.1021/jm00055a006

文献信息

• Synthesis and antiviral activity of 3'-deoxy-3'-C-hydroxymethyl nucleosides
  作者：Mark J. Bamford、Paul L. Coe、Richard T. Walker

  DOI：10.1021/jm00171a025

  日期：1990.9

  allowed high yielding hydrolysis of the 3'-function to give the 3'-deoxy-3'-C-formyl-beta-D-arabino-pentofuranosyl nucleosides 21 and 22. Desilylation afforded the 1-(3-deoxy-3-C-formyl-beta- D-lyxo-pentofuranosyl) 3',5'-O-hemiacetal nucleosides 33 and 34, respectively. Reduction of the formyl group of 21 and 22, followed by desilylation, yielded the 3'-deoxy-3'-C-(hydroxymethyl)-beta-D-arabino- pentofuranosyl)

  已经合成了一系列的3'-支链糖核苷，特别是3'-脱氧-3'-C-羟甲基核苷，并将其评估为抗病毒剂。尿嘧啶和胸腺嘧啶的1-（2,3-环氧-5-O-三苯甲基-β-D-lyxo-五氟呋喃糖基）衍生物12和13分别与5,6-二氢-2-lithio-5-甲基-1,3,5-二噻嗪14分别提供相应的3'-官能化核苷15和16。用叔丁基二苯基甲硅烷基取代三苯甲基可高产率地水解3'-官能团，得到3'-脱氧-3'-C-甲酰基-β-D-阿拉伯糖基-戊呋喃糖基核苷21和22。甲硅烷基化得到1-（ 3-脱氧-3-C-甲酰基-β-D-lyxo-戊呋喃糖基）3'，5'-O-半缩醛核苷33和34。还原21和22的甲酰基，然后进行甲硅烷基化，分别产生3'-脱氧-3'-C-（羟甲基）-β-D-阿拉伯糖基-呋喃呋喃糖基）类似物7和8。将7的尿嘧啶碱基部分转化为5-碘尿嘧啶，然后转化为（E）-5-（2-溴乙烯基）尿嘧啶，以提供B
• BAMFORD, MARK J.;COE, PAUL L.;WALKER, RICHARD T., J. MED. CHEM., 33,(1990) N, C. 2494-2501
  作者：BAMFORD, MARK J.、COE, PAUL L.、WALKER, RICHARD T.

  DOI：——

  日期：——
• Syntheses and biological evaluations of 3'-deoxy-3'-C-branched-chain-substituted nucleosides
  作者：Tai Shun Lin、Ju Liang Zhu、Ginger E. Dutschman、Yung Chi Cheng、William H. Prusoff

  DOI：10.1021/jm00055a006

  日期：1993.2

  Various 3'-deoxy-3'-C-(hydroxymethyl)-, 3'-deoxy-3'-C-(fluoromethyl)-, 3'-deoxy-3'-C-(azidomethyl)-, and 3'-deoxy-3'-C-(aminomethyl)-substituted nucleosides (total 12 compounds) have been synthesized and evaluated against L1210, P388, S-180, and CCRF-CEM cells and HSV-1, HSV-2, and HIV-1 in culture. Only 3'-deoxy-3'-C-(hydroxymethyl)thymidine (36) was found to show significant anticancer activity against L1210, P388, S-180, and CCRF-CEM cells with ED50 values of 50, 5, 10, and 1 muM, respectively. None of these compounds demonstrated significant antiviral activity against HSV-1, HSV-2, or HIV-1. These compounds were also evaluated against thymidine kinases derived from HSV-1 (strain KOS), HSV-2 (strain 333), and mammalian (K562) cells. The thymidine kinase (HSV-1 strain KOS) was inhibited significantly by both 3'-deoxy-3'-C-(hydroxymethyl)- and 3'-deoxy-3'-C-(fluoromethyl)thymidine.