溴夫定杂质H | 69304-48-9

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 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: 溴夫定杂质H
• 英文名称: [125I]-(E)-5-(2-Iodovinyl)-2'-deoxyuridine
• 英文别名: (E)-5-(2-iodovinyl)-2'-deoxyuridine；1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-5-((E)-2-iodovinyl)pyrimidine-2,4(1H,3H)-dione；5-(2-iodo-vinyl)-2'-deoxy-uridine；E-5-(2-iodovinyl)-2'-deoxyuridine；E-5-(2-iodovinyl)-2'deoxyuridine；1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[(E)-2-iodoethenyl]pyrimidine-2,4-dione
• CAS: 69304-48-9
• 化学式: C₁₁H₁₃IN₂O₅
• 分子量: 380.139
• InChiKey: LOLNFJHUEIDGNH-PIXDULNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  溴夫定杂质H 生成 5-(1-hydroxy-2,2-diiodoethyl)-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione;trihydrate
  参考文献：
  名称：

  KUMAR, RAKESH;XU, LIHUA;KNAUS, EDWARD E.;WIEBE, LEONARD I.;TOVELL, DOROTH+, J. MED. CHEM., 33,(1990) N, C. 717-723

  摘要：

  DOI：
• 作为产物：
  描述：

  碘苷 在 bis-triphenylphosphine-palladium(II) chloride 、 一氯化碘 作用下， 以 乙腈 为溶剂， 反应 16.5h， 生成 溴夫定杂质H
  参考文献：
  名称：

  Synthesis and Cellular Uptake of 2‘-Substituted Analogues of (E)-5-(2-[¹²⁵I]Iodovinyl)-2‘-deoxyuridine in Tumor Cells Transduced with the Herpes Simplex Type-1 Thymidine Kinase Gene. Evaluation as Probes for Monitoring Gene Therapy

  摘要：

  A useful synthetic methodology was developed to synthesize and radiolabel a series of (E)-5-(2-[I-125]iodovinyl)uracil nucleoside substrates for herpes simplex virus type-1 thymidine kinase (HSV-1 TK). (E)-5-(2-[I-125]Iodovinyl)-2'-deoxyuridine ([I-125]IVDU, 10), (E)-5-(2-[I-125]iodovinyl)-2'-fluoro-2'-deoxyuridine ([I-125]IVFRU, 11), (E)-5-(2-[I-125]iodovinyl)-2'-fluoro-2'-deoxyarabinouridine ([I-125]IVFAU, 12), and (E)-5-(2-[I-125]iodovinyl)arabinouridine ([I-125]IVAU, 13) were synthesized in 63-83% radiochemical yield by reaction of the unprotected (E)-5-(2-(trimethylsilyl)vinyl) precursors (6-9) with [I-125]ICl. Cellular uptake of these labeled compounds (10-13) was evaluated in vitro. All compounds showed minimal uptake in the KBALB cell line. However, increased uptake was observed for all compounds in KBALB-STK cells which are transduced with a replication incompetent Moloney murine leukemia virus vector encoding the HSV-1 TK gene. The results indicate that uptake of these compounds in KBALB-STK cells is variable and highly dependent on the nature of the sugar 2'-substituent. When a fluoro (12) or a hydroxy (13) substituent is present in the arabinofuranosyl (up) configuration at the 2'-position, there is diminished cellular uptake in KBALB-STK cells relative to hydrogen (10) or fluorine (11) in the ribofuranosyl (down) configuration at the 2'-position. Our results indicate that radiolabeled IVFRU (11) is most promising for further in vivo studies.

  DOI：

  10.1021/jm9606406

文献信息

• Development of a general copper-catalyzed vinylic Finkelstein reaction—application to the synthesis of the C1–C9 fragment of laingolide B
  作者：Antoine Nitelet、Kévin Jouvin、Gwilherm Evano

  DOI：10.1016/j.tet.2016.07.018

  日期：2016.10

  conditions compatible with a range of highly functionalized substrates. The potential of this vinylic halogen exchange reaction in total synthesis and medicinal chemistry was demonstrated by its successful use for the synthesis of the C1–C9 fragment of laingolide B and for the late-stage modification of drug-like molecules. The extension of this halogen exchange to the acetylenic and allenic Finkelstein

  据报道，铜催化的乙烯基芬克尔斯坦反应的一种有效且广泛适用的方法。使用简单，易于获得且便宜的催化系统，可以将各种烯基碘化物和溴化物平稳地转化为它们的较低同系物，并具有高收率并完全保留双键的几何形状。这种乙烯基Finkelstein反应的关键特征是其广泛的适用性，使易得的链烯基碘化物转化为难得的溴代和氯代对应物，并且温和的反应条件与一系列高度官能化的底物相容。这种乙烯基卤素交换反应在全合成和药物化学中的潜力已通过成功地用于合成Laingolide B的C1-C9片段以及对药物样分子进行后期修饰而得到证明。还报道了这种卤素交换扩展到炔属和烯属的Finkelstein反应。
• Synthesis of some 5-halogenovinyl derivatives of uracil and their conversion into 2′-deoxyribonucleosides
  作者：Philip J. Barr、A. Stanley Jones、Gabriel Verhelst、Richard T. Walker

  DOI：10.1039/p19810001665

  日期：——

  gave (E)-5-(2-carboxyvinyl)uracil which, upon reaction with the appropriate N-halogenosuccinimide, gave (E)-5-(2-bromovinyl)uracil, (E)-5-(2-chlorovinyl)uracil, and (E)-5-(2-iodovinyl)uracil. The last mentioned compound was also obtained by the action of iodine chloride on 5-vinyluracil. 5-(1-Chlorovinyl)uracil upon treatment with bromine gave 5(2-bromo-1-chlorovinyl)uracil which reacted with sodium

  在哌啶存在下用丙二酸处理5-甲酰尿嘧啶，得到（E）-5-（2-羧基乙烯基）尿嘧啶，与适当的N-卤代琥珀酰亚胺反应后，得到（E）-5-（2-溴乙烯基）尿嘧啶。 ，（E）-5-（2-氯乙烯基）尿嘧啶和（E）-5-（2-碘乙烯基）尿嘧啶。最后提到的化合物也是通过氯化碘对5-乙烯基尿嘧啶的作用而获得的。用溴处理5-（1-氯丙炔基）尿嘧啶得到5（2-溴-1-氯乙烯基）尿嘧啶，其与甲醇钠反应得到5-溴乙炔基尿嘧啶。（E）-5-（2-溴乙烯基）-尿嘧啶转化为三甲基甲硅烷基衍生物，与2-脱氧-3,5-二-O-（p（-甲苯甲酰基）-α- D-赤-五呋喃糖酰氯，得到被保护的脱氧核糖核苷的α-和β-异头物。用甲醇钠除去对甲苯甲酰基保护基，得到（E）-5-（2-溴乙烯基）-1-（2-脱氧-α- D-赤型-戊呋喃糖基）尿嘧啶和（E）-5-（2-溴夫酰基）-2'-脱氧尿苷。一系列类似的反应，得到（Ë）-5-（2-碘乙
• 2'Deoxy-5-(2-halogenovinyl)-uridines, pharmaceutical compositions and
  申请人：Rega Instituut VZW

  公开号：US04424211A1

  公开（公告）日：1984-01-03

  The novel substance E-5-(2-bromovinyl)-2'-deoxyuridine and its corresponding iodovinyl derivative are gifted with specific antiviral activities towards herpes simplex virus. They may be synthesized by a condensation reaction followed by separation of anomers.

  新型物质E-5-(2-溴乙烯基)-2'-脱氧尿嘧啶及其对应的碘乙烯基衍生物具有特定的抗病毒活性，对单纯疱疹病毒有效。它们可以通过缩合反应合成，然后分离异构体。
• Synthesis and biological evaluation of 5-(1-alkoxy-2-haloethyl)-2′-deoxyuridines and related uracil analogues
  作者：Rakesh Kumar、Leonard I. Wiebe、E. E. Knaus、Mark L. Tempest

  DOI：10.1002/jhet.5570280206

  日期：1991.2

  A new class of 5-[1-alkoxy-2-iodo(or 2,2-diiodo)ethyl] derivatives of 2′-deoxyuridine and uracil were synthesized by a regiospecific reaction of the C-5 vinyl substituent with iodine monochloride and an alcohol. These compounds were either weak or inactive antiviral and inactive cytotoxic agents.

  通过C-5乙烯基取代基与一氯化碘和一价碘的对映体特异性反应，合成了2'-脱氧尿苷和尿嘧啶的一类新的5- [1-烷氧基-2-碘（或2，2-二碘代）乙基]衍生物。酒精。这些化合物是弱的或无活性的抗病毒和无活性的细胞毒剂。
• Synthesis of brain-targeted 5-iodo-, 5-vinyl- and (<i>E</i>)-5-(2-iodovinyl)-2′-deoxyuridines coupled to a dihydropyridine ⇌ pyridinium salt redox chemical delivery system
  作者：Rakesh Kumar、Gueijun Ji、Leonard I. Wiebe、Edward E. Knaus

  DOI：10.1002/jhet.5570280327

  日期：1991.4

  4-dihydropyridyl-3-carbonyl)-2′-deoxyuridine (15a), 5-vinyl-3′-O-(1-methyl-1,4-di-hydropyridyl-3-carbonyl)-2′-deoxyuridine (15b) and (E)-5-(2-iodovinyl)-3′-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-2′-deoxyuridine (15c) were synthesized for future evaluation as lipophilic brain-selective antiviral agents for the treatment of herpes simplex encephalitis. Quaternization of the 3′-O-(3-pyridylcarbonyl) compounds

  5-碘-3'- O-（1-甲基-1,4-二氢吡啶基-3-羰基）-2'-脱氧尿苷（15a），5-乙烯基-3'- O-（1-甲基-1,4 -二氢吡啶基-3-羰基）-2'-脱氧尿苷（15b）和（E）-5-（2-碘乙烯基）-3'- O-（1-甲基-1,4-二氢吡啶基-3-羰基）合成了-2'-脱氧尿苷（15c）作为用于治疗单纯疱疹性脑炎的亲脂性脑选择性抗病毒药，以供将来评估。使用碘甲烷对3'- O-（3-吡啶基羰基）化合物10-11进行季铵化，得到相应的1-甲基吡啶鎓盐12-13用连二亚硫酸钠还原，得到相应的3' - O-（1-甲基-1,4-二氢吡啶基-3-羰基）化合物14-15。