1-[(2R,4S,5S)-4-叠氮基-5-(羟基甲基)四氢呋喃-2-基]-5-甲基-4-巯基嘧啶-2-酮 | 108441-45-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: 1-[(2R,4S,5S)-4-叠氮基-5-(羟基甲基)四氢呋喃-2-基]-5-甲基-4-巯基嘧啶-2-酮
• 英文名称: 3'-azido-3'-deoxy-4-thio-β-D-thymidine
• 英文别名: 3'-Azido-3'-deoxy-4-thiothymidine；1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-4-sulfanylidenepyrimidin-2-one
• CAS: 108441-45-8
• 化学式: C₁₀H₁₃N₅O₃S
• 分子量: 283.311
• InChiKey: LQGXMSIIZGFDND-XLPZGREQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-[(2R,4S,5S)-4-叠氮基-5-(羟基甲基)四氢呋喃-2-基]-5-甲基-4-巯基嘧啶-2-酮 、 5'-Acetyl-3'-azido-2',3'-dideoxy-5-iodouridine 、 三甲基乙炔基硅 在 双三苯基磷二氯化钯 、 碘化亚铜 1-(4-azido-5-hydroxymethyl-tetrahydrofuran-2-yl)-5-ethynyl-1H-pyrimidine-2,4-dione 、 三乙胺 、 氮气 、 氯仿 、 乙二胺四乙酸 、 Sodium sulfate-III 、 sodium methylate 、 甲醇 、 H+ 、 silica gel 、 chloroform methanol 作用下， 反应 5.0h， 以yields the title compound as a solid, 80 mg(0.29 mMol, 30%)的产率得到1-(4-azido-5-hydroxymethyl-tetrahydrofuran-2-yl)-5-ethynyl-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Therapeutic nucleosides

  摘要：

  本文介绍了几种新型的3-叠氮基-2,3-二去氧-β-D-鼠李糖-戊糖衍生物，这些衍生物是取代嘧啶酮的抗逆转录病毒，特别是抗艾滋病活性。

  公开号：

  US05064946A1
• 作为产物：
  描述：

  5'-O-acetyl-3'-azido-3'-deoxythymidine 在 劳森试剂 、 甲醇 、 氨 作用下， 以 甲苯 为溶剂， 反应 6.0h， 生成 1-[(2R,4S,5S)-4-叠氮基-5-(羟基甲基)四氢呋喃-2-基]-5-甲基-4-巯基嘧啶-2-酮
  参考文献：
  名称：

  Synthesis and inhibitory activity of thymidine analogues targeting Mycobacterium tuberculosis thymidine monophosphate kinase

  摘要：

  We report on Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) inhibitory activities of a series of new 3'- and 5'-modified thymidine analogues including alpha- and beta-derivatives. In addition, several analogues were synthesized in which the 4-oxygen was replaced by a more lipophilic sulfur atom to probe the influence of this modification on TMPKmt inhibitory activity. Several compounds showed an inhibitory potency in the low micromolar range, with the 5'-arylthiourea 4-thio-alpha-thymidine analogue being the most active one (K(i) = 0.17 mu M). This compound was capable of inhibiting mycobacteria growth at a concentration of 25 mu g/mL. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.021

文献信息

• Synthesis and in vitro evaluation of some modified 4-thiopyrimidine nucleosides for prevention or reversal of AIDS - associated neurological disorders
  作者：Eduardo Palomino、Bernard R. Meltsner、David Kessel、Jerome P. Horwitz

  DOI：10.1021/jm00163a043

  日期：1990.1

  developed for the initial synthesis of AZT. Thiation of 2',3'-didehydro-3'-deoxythymidine (4a) and 2',3'-didehydro-2',3'-dideoxyuridine (4c) was carried out with Lawesson's reagent on the corresponding 5'-O-benzoate esters, 4b and 4d, to give 5a and 5c, respectively. The latter, on alkaline hydrolysis, gave 2',3'-didehydro-3'-deoxy-4-thiothymidine (5b) and 2',3'-didehydro-2',3'-dideoxyuridine (5d), respectively

  描述了几个修饰的嘧啶核苷（包括3'-叠氮基3'-脱氧胸苷（AZT））在C-4羰基上的氧-硫交换，目的是增强亲脂性，从而传递至中枢神经系统在不损害亲本结构的抗HIV活性的前提下制备出类似的硫磺类似物。从4-硫代胸苷（1）开始制备3'-叠氮基-3'-脱氧-4-硫代胸腺嘧啶（3），并采用了用于AZT初始合成的相同方法。用Lawesson试剂在相应的5'-O-上进行2'，3'-二氢-3'-脱氧胸苷（4a）和2'，3'-二氢-2'，3'-二脱氧尿苷（4c）的亚硫酰化。苯甲酸酯4b和4d分别得到5a和5c。后者经碱水解，得到2'，3'-二氢-3' -脱氧-4-硫代胸苷（5b）和2'，3'-二氢-2'，3'-二脱氧尿苷（5d）。将相同系列的反应应用于2'，3'-二脱氧尿苷（6a）和3'-脱氧胸苷（6b）的5'-O-苯甲酸酯，得到2'，3'-二脱氧-4-硫尿苷（7d ）和3'-脱氧-4-硫代胸苷（7b）。
• PALOMINO, EDUARDO;MELTSNER, BERNARD R.;KESSEL, DAVID;HORWITZ, JEROME P., J. MED. CHEM., 33,(1990) N, C. 258-263
  作者：PALOMINO, EDUARDO、MELTSNER, BERNARD R.、KESSEL, DAVID、HORWITZ, JEROME P.

  DOI：——

  日期：——
• US5064946A
  申请人：——

  公开号：US5064946A

  公开（公告）日：1991-11-12
• Synthesis and inhibitory activity of thymidine analogues targeting Mycobacterium tuberculosis thymidine monophosphate kinase
  作者：Sara Van Poecke、Hélène Munier-Lehmann、Olivier Helynck、Matheus Froeyen、Serge Van Calenbergh

  DOI：10.1016/j.bmc.2011.10.021

  日期：2011.12

  We report on Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) inhibitory activities of a series of new 3'- and 5'-modified thymidine analogues including alpha- and beta-derivatives. In addition, several analogues were synthesized in which the 4-oxygen was replaced by a more lipophilic sulfur atom to probe the influence of this modification on TMPKmt inhibitory activity. Several compounds showed an inhibitory potency in the low micromolar range, with the 5'-arylthiourea 4-thio-alpha-thymidine analogue being the most active one (K(i) = 0.17 mu M). This compound was capable of inhibiting mycobacteria growth at a concentration of 25 mu g/mL. (C) 2011 Elsevier Ltd. All rights reserved.
• Therapeutic nucleosides
  申请人：Burroughs Wellcome Co.

  公开号：US05064946A1

  公开（公告）日：1991-11-12

  Several novel 3-azido-2,3-dideoxy-.beta.-D-erythro-pentofuranosyl derivatives of substituted pyrimidinones having antiretroviral, especially anti-AIDS, activity are described.

  本文介绍了几种新型的3-叠氮基-2,3-二去氧-β-D-鼠李糖-戊糖衍生物，这些衍生物是取代嘧啶酮的抗逆转录病毒，特别是抗艾滋病活性。