1-(2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl)-5-iodo-uracil | 144989-72-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 1-(2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl)-5-iodo-uracil
• 英文别名: 1-(2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl)-5-iodouracil；2',3'-didehydro-2',3'-dideoxy-5-iodouridine；Uridine, 2',3'-didehydro-2',3'-dideoxy-5-iodo-；1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-5-iodopyrimidine-2,4-dione
• CAS: 144989-72-0
• 化学式: C₉H₉IN₂O₄
• 分子量: 336.086
• InChiKey: NMXNXIYEWKFGMD-CAHLUQPWSA-N

物化性质

• 密度：
  2.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl)-5-iodo-uracil 、 p-methylphenyl methoxyalaninyl phosphorochloridate 在 N-甲基咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以35%的产率得到methyl ((((2S,5R)-5-(5-iodo-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methoxy)(p-tolyloxy)phosphoryl)-L-alaninate
  参考文献：
  名称：

  [d4U]-Spacer-[HI-236] HIV-1 逆转录酶双药抑制剂

  摘要：

  [d4U]-间隔基-[HI-236] 类型的四种双药 HIV NRTI/NNRTI 抑制剂15a – d，其中间隔基变化为 1-丁炔基 ( 15a )、炔丙基-1-PEG ( 15b )、炔丙基-2-PEG ( 15c ) 和炔丙基-4-PEG ( 15d ) 已被合成并作为抗 HIV-1 的 RT 抑制剂进行生物学评估。他们合成的关键步骤涉及 5-碘 d4U 苯甲酸酯与炔基化 HI-236 前体的 Sonogashira 偶联，然后引入 HI-236 硫脲官能团。细胞培养（MT-2 细胞）以及使用体外 RT 测定的生物学评估显示15a – c比 d4T 更活跃。然而，总体而言，结果表明衍生物作为链延长的 NNRTIs，其中对于15b - d，核苷组分可能位于口袋外，但没有证据表明 NRTI 和 NNRTI 位点之间存在任何协同双结合。这部分归因于由于激酶识别失败导致双药核苷组分缺乏磷酸化，而结合

  DOI：

  10.1016/j.bmc.2010.05.025
• 作为产物：
  描述：

  碘苷 在 吡啶 、 sodium hydroxide 、 potassium tert-butylate 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 14.75h， 生成 1-(2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl)-5-iodo-uracil
  参考文献：
  名称：

  5-取代的嘧啶核苷的合成及其体外抗分枝杆菌活性。

  摘要：

  结核分枝杆菌和鸟分枝杆菌感染是两个最重要的分枝杆菌，导致艾滋病患者的死亡率增加。各种5-取代的2'-脱氧尿苷，尿苷，2'-O-甲基尿苷，2'-核氟-2'-脱氧尿苷，3'-取代的2'，3'-二脱氧尿苷，2'，3'-二脱氧尿苷合成了2′，3′-二脱氢-2′，3′-二脱氧尿苷，并评价了它们对牛分枝杆菌和鸟分枝杆菌的体外抑制活性。5-（C-1取代）-2'-脱氧尿苷衍生物作为鸟分枝杆菌的有效抑制剂出现（MIC90 = 1-5 microg / mL范围）。2'-脱氧尿苷系列中C-5取代基的性质似乎是抗分枝杆菌活性的决定因素。

  DOI：

  10.1016/j.bmc.2005.07.046

文献信息

• Synthesis of 2,3’-Anhydro-2’-deoxyuridines and 2’,3’-Didehydro-2’,3’-dideoxyuridines Using Polymer Supported Fluoride
  作者：Erik Larsen、Thomas Kofoed、Erik B. Pedersen

  DOI：10.1055/s-1995-4070

  日期：1995.9

  Reaction of methyl 5-O-tert-butyldiphenylsilyl-2-deoxy-3-O-p-toluenesulfonyl-α,β-D-erythro-pentofuranoside (2) with silylated uracils 3 using trimethylsilyl trifluoromethanesulfonate (TMS triflate) as catalyst afforded after crystallization in Et2O the corresponding β-nucleosides 4. Reaction of 4 with tetrabutylammonium fluoride (TBAF) or Amberlyst A-26 resin (F--form) in THF at room temperature or at reflux gave the corresponding deprotected 2,3’-anhydro-2’-deoxyuridines 6 and 2’,3’-didehydro-2’,3’-dideoxyuridines 7, respectively.

  以三氟甲磺酸三甲基硅酯（TMS triflate）为催化剂，5-O-叔丁基二苯基硅烷-2-脱氧-3-O-对甲苯磺酰基-δ，δ-D-赤式戊呋喃糖苷（2）与硅烷基化的尿嘧啶 3 反应，在 Et2O 中结晶后得到相应的δ-核苷 4。在室温或回流条件下，将 4 与四丁基氟化铵（TBAF）或 Amberlyst A-26 树脂（F--form）在 THF 中反应，可分别得到相应的去保护的 2,3'-脱氢-2'-脱氧尿苷 6 和 2',3'-二脱氢-2',3'-二脱氧尿苷 7。
• Joshi, Bhalchandra V.; Rao, T. Sudhakar; Reese, Colin B., Journal of the Chemical Society. Perkin transactions I, 1992, # 19, p. 2537 - 2544
  作者：Joshi, Bhalchandra V.、Rao, T. Sudhakar、Reese, Colin B.

  DOI：——

  日期：——
• Potential Multifunctional Inhibitors of HIV-1 Reverse Transcriptase. Novel [AZT]-[TSAO-T] and [d4T]-[TSAO-T] Heterodimers Modified in the Linker and in the Dideoxynucleoside Region
  作者：Sonsoles Velázquez、Victoria Tuñón、María Luisa Jimeno、Cristina Chamorro、Erik De Clercq、Jan Balzarini、María José Camarasa

  DOI：10.1021/jm991092+

  日期：1999.12.1

  In an attempt to combine the anti-HIV-inhibitory capacity of nucleoside reverse transcriptase (RT) inhibitors (NRTI) and non-nucleoside RT inhibitors (NNRTI), several heterodimer analogues of the previously reported [AZT]-(CH(2))(3)-[TSAO-T] prototype have been prepared. In these novel series, other NRTIs, an expanded range of linkers with different conformational freedom and other attachment sites for these linkers on the base part of the NRTI analogue have been explored. Moreover, in order to circumvent the dependence of the NRTI moiety of the heterodimer an activation by cellular nucleoside kinases, novel heterodimers in which the NRTI is bearing a masked monophosphate group at the 5'-position are described. Among the novel heterodimers, several derivatives show a potent anti-HIV-1 activity, which proved comparable, or even superior, to that of the AZT heterodimer prototype. The nature of the NRTI was important far the eventual anti-HIV-1 activity. In particular, the d4T heterodimer derivative containing a propyl linker between the N-3 positions of the base of TSAO-T and d4T was similar to 5- to 10-fold more inhibitory to HIV-1 than the corresponding AZT heterodimer prototype.
• SYNTHESIS OF 5-ALKENYLATED D4T ANALOGUES VIA THE Pd-CATALYZED CROSS-COUPLING REACTION
  作者：A. Ciurea、C. Fossey、S. Benzaria、D. Gavriliu、Z. Delbederi、B. Lelong、D. Ladurée、A. M. Aubertin、A. Kirn

  DOI：10.1081/ncn-100105902

  日期：2001.9.30

  The target compounds 5-[N-(6-amino-hexyl)-acrylamide]-2 ' ,3 ' -didehydro-2 ' ,3 ' -dideoxy-uridine (12) and 5-N-[5-(methoxycarbonyl)-pentyl]acrylamide}-2 ' ,3 ' -didehydro-2',3 ' -dideoxy-uridine (15) were prepared by the palladium acetate-triphenylphosphine-catalyzed reaction of the 5 ' -O-acetyl-5-iodo-d4T analogue (3). These compounds 12 and 15 can be used to prepare nucleotide probes carrying fluorescent labels and were nevertheless screened for their anti-HIV activity. The biological data demonstrated that none of them were active against HIV-1.
• HALO-DEHYDRO-3'-DEOXYURACIL PHOSPHORAMIDATES AND RELATED COMPOUNDS AND THEIR USE IN TREATING MEDICAL CONDITIONS
  申请人：[en]ROME THERAPEUTICS, INC.

  公开号：WO2024107850A1

  公开（公告）日：2024-05-23

  Substituted halo-dehydro-3'-deoxyuracil phosphoramidates and related compounds, pharmaceutical compositions, their use for inhibiting LINE1 reverse transcriptase and/or HERV-K reverse transcriptase activity, and their use in the treatment of medical disorders, such as cancer, are disclosed herein.