1-<3-deoxy-3-C-(fluoromethyl)-β-D-arabino-pentofuranosyl>thymine | 129678-58-6

• 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-(fluoromethyl)-β-D-arabino-pentofuranosyl>thymine
• 英文别名: 1-<3-C-(fluoromethyl)-3-deoxy-β-D-threo-pentofuranosyl>thymine；1-[(2R,3S,4S,5S)-4-(fluoromethyl)-3-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-5-methyl-pyrimidine-2,4-dione；1-[(2R,3S,4S,5S)-4-(fluoromethyl)-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 129678-58-6
• 化学式: C₁₁H₁₅FN₂O₅
• 分子量: 274.249
• InChiKey: ZHALTLRSOULQAM-BDNRQGISSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 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：
  99.1
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ((3aR,5S,6R,6aR)-tetrahydro-2,2-dimethyl-5-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)furo[2,3-d][1,3]dioxol-6-yl)methanol 在 palladium on activated charcoal 吡啶 、 sodium hydroxide 、 sodium tetrahydroborate 、 sodium periodate 、 二甲氨基三氟化硫 、 C₄F₉SO₃K 、 硫酸 、 氨 、 氢气 、 sodium hydride 、 碳酸氢钠 、 六甲基二硅氮烷 、 三氟乙酸 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 97.75h， 生成 1-<3-deoxy-3-C-(fluoromethyl)-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 some 3'-C-difluoromethyl- and 3'-deoxy-3'-C-fluoromethyl nucleosides
  作者：Mark J. Bamford、Paul L. Coe、Richard T. Walker

  DOI：10.1021/jm00171a024

  日期：1990.9

  The synthesis and antiviral activity of a number of 3'-C-difluoromethyl and 3'-deoxy-3'-C-fluoromethyl nucleosides are reported. The 3'-C-difluoromethyl nucleosides 26a and 26b were obtained by treatment of the corresponding 2',5'-di-O-protected-3'-C-formyl nucleosides 25a and 25b with (diethylamino)sulfur trifluoride (DAST). Removal of the 2'-O-protecting group from 26a and subsequent reaction with

  报道了许多3'-C-二氟甲基和3'-脱氧-3'-C-氟甲基核苷的合成和抗病毒活性。通过用（二乙基氨基）三氟化硫（DAST）处理相应的2'，5'-二-O-保护的-3'-C-甲酰基甲酰基核苷25a和25b，获得3'-C-二氟甲基核苷26a和26b。从26a除去2'-O-保护基，然后与DAST反应，得到2'-脱氧-2'-氟-β-D-核糖-戊呋喃糖基核苷29。用DAST对5'-O-进行选择性氟化保护的类似物3'-脱氧-3'-C-羟甲基衍生物13a和13b得到3'-脱氧-3'-C-氟甲基衍生物30a和30b，而非选择性氟化得到2'，3'-二脱氧-2' -氟-3'-C-氟甲基类似物31a和31b。将去保护的尿嘧啶类似物17a碘化为5-碘尿嘧啶衍生物18。评估了完全去保护的氟化的3'-C-分支的核苷14-18和32的抗病毒活性。在浓度高达100 microM的情况下，没有一种对人类1型免疫缺陷病毒（HI
• VINNICHENKO, A. I.;LIVENSKAYA, O. A.;TSURKAN, I. V., XIMIYA PRIROD. SOED.,(1990) N, S. 842-844
  作者：VINNICHENKO, A. I.、LIVENSKAYA, O. A.、TSURKAN, I. V.

  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.