5-(dodec-1-ynyl)-2'-deoxyuridine | 215668-76-1

• 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-(dodec-1-ynyl)-2'-deoxyuridine
• 英文别名: 5-dodecynyl-2'-deoxyuridine；5-dodec-1-ynyl-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 215668-76-1
• 化学式: C₂₁H₃₂N₂O₅
• 分子量: 392.495
• InChiKey: PGRIBSVBDKBPAD-IPMKNSEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 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：

  5-(dodec-1-ynyl)-2'-deoxyuridine 在 磷酸三甲酯 、 三氯氧磷 作用下， 反应 2.0h， 以24%的产率得到5-(dodec-1-ynyl)-2'-deoxyuridine-5'-monophosphate disodium salt
  参考文献：
  名称：

  5取代的2'-脱氧尿苷单磷酸酯类似物作为黄素依赖性胸苷酸合酶抑制剂在结核分枝杆菌中的合成和评价

  摘要：

  一系列5-取代的2'-脱氧尿苷一磷酸类似物已被合成并评价为分枝杆菌ThyX的潜在抑制剂，以一种新颖的依赖黄素的胸苷酸合酶的结核分枝杆菌。一项系统的SAR研究导致鉴定了化合物5a，相对于分枝杆菌ThyX，IC 50值为0.91μM。该衍生物对经典的分枝杆菌胸苷酸合酶ThyA（IC 50 > 50μM）缺乏活性，是选择性分枝杆菌FDTS抑制剂的第一个实例。

  DOI：

  10.1021/jm2004688
• 作为产物：
  描述：

  1-十二炔 、 碘苷 在 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 以58%的产率得到5-(dodec-1-ynyl)-2'-deoxyuridine
  参考文献：
  名称：

  5取代的2'-脱氧尿苷单磷酸酯类似物作为黄素依赖性胸苷酸合酶抑制剂在结核分枝杆菌中的合成和评价

  摘要：

  一系列5-取代的2'-脱氧尿苷一磷酸类似物已被合成并评价为分枝杆菌ThyX的潜在抑制剂，以一种新颖的依赖黄素的胸苷酸合酶的结核分枝杆菌。一项系统的SAR研究导致鉴定了化合物5a，相对于分枝杆菌ThyX，IC 50值为0.91μM。该衍生物对经典的分枝杆菌胸苷酸合酶ThyA（IC 50 > 50μM）缺乏活性，是选择性分枝杆菌FDTS抑制剂的第一个实例。

  DOI：

  10.1021/jm2004688

文献信息

• 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.
• Bicyclic anti-VZV nucleosides: Thieno analogues retain full antiviral activity
  作者：Andrea Brancale、Christopher McGuigan、Berthe Algain、Pascal Savy、Rachid Benhida、Jean-Louis Fourrey、Graciela Andrei、Robert Snoeck、Erik De Clercq、Jan Balzarini

  DOI：10.1016/s0960-894x(01)00471-1

  日期：2001.9

  Thieno analogues of the potent and selective furo-pyrimidine anti-VZV nucleoside family are herein reported. The compounds retain full antiviral potency in comparison to the furo parent. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Potent and Selective Inhibition of Varicella-Zoster Virus (VZV) by Nucleoside Analogues with an Unusual Bicyclic Base
  作者：Christopher McGuigan、Christopher J. Yarnold、Garry Jones、Sonsoles Velázquez、Hubert Barucki、Andrea Brancale、Graciela Andrei、Robert Snoeck、Erik De Clercq、Jan Balzarini

  DOI：10.1021/jm990346o

  日期：1999.11.1

  We herein report the discovery of an entirely new category of potent antiviral agents based on novel deoxynucleoside analogues with unusual bicyclic base moieties. Target structures, previously known as byproducts in Pd-catalyzed coupling of terminal alkynes with 5-iodo-nucleosides, are recognized herein for the first time to be potent and selective inhibitors of varicella-zoster virus (VZV) in vitro. As an unusual structure-activity relationship we noted the absolute requirement of a long alkyl side chain, with an optimum length of C-8-C-10, for antiviral activity. We thus report the synthesis and characterization of a series of chain-modified analogues and their extensive in vitro evaluation. The lead compounds have a ca. 300-fold enhancement in anti-VZV activity over the reference compound acyclovir, with no detectable in vitro cytotoxicity. The novel structure of these compounds, coupled with their ease of synthesis, excellent antiviral profile, and promising physical properties, makes them of great interest for possible antiviral drug development.
• ANTI-VIRAL PYRIMIDINE NUCLEOSIDE ANALOGUES
  申请人：University College Cardiff Consultants Limited

  公开号：EP0980377B1

  公开（公告）日：2002-07-31
• US6573247B1
  申请人：——

  公开号：US6573247B1

  公开（公告）日：2003-06-03