5-ethynyltrimethylsilyl-3',5'-di-O-p-toluyl-2'-deoxyuridine | 77875-91-3

• 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: 5-ethynyltrimethylsilyl-3',5'-di-O-p-toluyl-2'-deoxyuridine
• 英文别名: 2'-Deoxy-3',5'-di-O-p-toluoyl-5-(2-trimethylsilylethynyl)uridine；2'-Deoxy-5-[2-(trimethylsilyl)ethynyl]-uridine 3',5'-Bis(4-methylbenzoate)；[(2R,3S,5R)-5-[2,4-dioxo-5-(2-trimethylsilylethynyl)pyrimidin-1-yl]-3-(4-methylbenzoyl)oxyoxolan-2-yl]methyl 4-methylbenzoate
• CAS: 77875-91-3
• 化学式: C₃₀H₃₂N₂O₇Si
• 分子量: 560.679
• InChiKey: FDKOXQWIFHEWKM-JIMJEQGWSA-N

物化性质

• 熔点：
  >243C (dec.)
• 溶解度：
  DMSO（稍微加热）

计算性质

• 辛醇/水分配系数(LogP)：
  3.75
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-ethynyltrimethylsilyl-3',5'-di-O-p-toluyl-2'-deoxyuridine 在 palladium on activated charcoal 氢气 、 sodium methylate 作用下， 以 甲醇 、 乙醇 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 7.0h， 生成 乙去氧尿啶
  参考文献：
  名称：

  Nucleic acid related compounds. 39. Efficient conversion of 5-iodo to 5-alkynyl and derived 5-substituted uracil bases and nucleosides

  摘要：

  DOI：

  10.1021/jo00159a012
• 作为产物：
  描述：

  5-iodo-3',5'-di-O-p-toluyl-2'-deoxyuridine 、 三甲基乙炔基硅 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 作用下， 以 三乙胺 为溶剂， 反应 18.0h， 以85%的产率得到5-ethynyltrimethylsilyl-3',5'-di-O-p-toluyl-2'-deoxyuridine
  参考文献：
  名称：

  核酸相关化合物。31.末端炔烃与5-碘尿嘧啶核苷的平滑高效钯钯催化偶联

  摘要：

  在三乙胺中存在二氯双（三苯基膦）钯和碘化铜（I）的情况下，末端炔烃与受保护的5-碘尿嘧啶核苷的偶联以72-92％的收率得到相应的5-（炔-1-基）尿嘧啶核苷。

  DOI：

  10.1016/0040-4039(81)80115-3

文献信息

• 2'-deoxy-5-ethynyluridine-3',5'-diestens for treatment of VZV and CMV
  申请人：Burroughs Wellcome Co.

  公开号：US04863906A1

  公开（公告）日：1989-09-05

  The present invention relates to the use of 2'-deoxy-5-ethynyluridine and its pharmaceutically acceptable derivatives in the treatment and prophylaxis of varicella zoster virus and cytomegalovirus infections. Also provided are pharmaceutical formulations and processes for the preparation of the compounds according to the invention.

  本发明涉及在水痘带状疱疹病毒和巨细胞病毒感染的治疗和预防中使用2'-脱氧-5-乙炔尿苷及其药用可接受衍生物。还提供了根据本发明制备化合物的药物配方和过程。
• Design and Studies of Novel 5-Substituted Alkynylpyrimidine Nucleosides as Potent Inhibitors of Mycobacteria
  作者：Dinesh Rai、Monika Johar、Tracey Manning、B. Agrawal、Dennis Y. Kunimoto、Rakesh Kumar

  DOI：10.1021/jm058167w

  日期：2005.11.1

  We herein report a new category of 5-substituted pyrimidine nucleosides as potent inhibitors of mycobacteria. A series of 5-alkynyl derivatives of 2'-deoxyuridine (1-8), 2'-deoxycytidine (9-14), uridine (15-17), and 2'-O-methyluridine (18, 19) were synthesized and evaluated for their antimycobacterial activity in vitro. 5-Decynyl, 5-dodecynyl, and 5-tetradecynyl derivatives showed the highest antimycobacterial potency against M. bovis and M. avium, with the 2'-deoxyribose derivatives being more effective than the ribose analogues. Nucleosides bearing short alkynyl side chains 5-ethynyl, 5-propynyl, 5-pentynyl, and 5-heptynyl were mostly not inhibitory. Incorporation of a phenylethynyl function at the 5-position diminished the antimicrobial effect. Furthermore, related bicyclic analogues (20-24) were devoid of antimycobacterial activity, indicating that an acyclic side chain at the C-5 position of the pyrimidine ring is essential for potent activity. Compounds 1-17 were synthesized by the Pd-catalyzed coupling reactions of respective alkynes with 5-iodo derivatives of 2'-deoxyuridine, 2'-deoxycytidine, and uridine. Intramolecular cyclization of 1 and 3-6 in the presence of Cu afforded the corresponding bicyclic compounds 20-24. The investigated nucleosides are recognized here for the first time to be potent inhibitors of mycobacteria. This class of compounds could be of interest for lead optimization as antimycobacterial agents.
• Antiviral compounds
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0208550B1

  公开（公告）日：1991-05-22
• Synthesis of tricarbonyl rhenium and technetium complexes of a 5′-carboxamide 5-ethyl-2′-deoxyuridine for selective inhibition of herpes simplex virus thymidine kinase 1
  作者：D. Desbouis、P.A. Schubiger、R. Schibli

  DOI：10.1016/j.jorganchem.2006.10.011

  日期：2007.2

  Herpes simplex virus thymidine kinase type 1 (HSV1-TK) is frequently used as reporter protein in gene therapy. Our aim is to produce single photon emitting reporter probe based on technetium-99m. The synthesis of organometallic technetium and rhenium complexes of a 5'-carboxamide 5-ethyl-2'-deoxyuridine derivative able to selectively inhibit HSV1-TK is presented. The 5-ethyl-2'-deoxyuridine functionalized with a suitable tridentate chelating system at position 5' was synthesized from commercial 2'-deoxyuridine in seven steps. The 5-ethyl-2'-deoxyuridine derivative was labeled with the fac-M(CO)(3)-core (M = Tc, Re). The resulting rhenium complex was found to be a selective competitive inhibitor of HSV1-TK (K-i = 4.56 mu M). Inhibition of the human cytosolic thymidine kinase (hTK1) previously reported with organometallic rhenium and technetium complexes of 5'-carboxamide thymidine derivative was not observed. The uptake of the technetium-99m complex in transfected cells expressing HSV1-TK has been evaluated to assess its possible use as reporter. (C) 2006 Elsevier B.V. All rights reserved.
• Nucleic acid related compounds. 31. Smooth and efficient palladium-copper catalyzed coupling of terminal alkynes with 5-iodouracil nucleosides
  作者：Morris J. Robins、Philip J. Barr

  DOI：10.1016/0040-4039(81)80115-3

  日期：1981.1

  Coupling of terminal alkynes with protected 5-iodouracil nucleosides in the presence of dichlorobis(triphenylphosphine)palladium and copper(I) iodide in triethylamine gives the corresponding 5-(alkyn-1-yl)uracil nucleosides in 72–92% yields.

  在三乙胺中存在二氯双（三苯基膦）钯和碘化铜（I）的情况下，末端炔烃与受保护的5-碘尿嘧啶核苷的偶联以72-92％的收率得到相应的5-（炔-1-基）尿嘧啶核苷。