5-tetradecynyl-2'-deoxyuridine | 215668-75-0

• 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-tetradecynyl-2'-deoxyuridine
• 英文别名: 4-hydroxy-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-5-tetradec-1-ynyl-pyrimidin-2-one；1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-tetradec-1-ynylpyrimidine-2,4-dione
• CAS: 215668-75-0
• 化学式: C₂₃H₃₆N₂O₅
• 分子量: 420.549
• InChiKey: WRZPEEWYUHHKPC-PWRODBHTSA-N

物化性质

• 密度：
  1.18±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  30
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.74
• 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-tetradecynyl-2'-deoxyuridine 在 TEA 、 硫代乙酸 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 26.0h， 生成 6-Dodecyl-3-((2R,4S,5R)-4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-3H-thieno[2,3-d]pyrimidin-2-one
  参考文献：
  名称：

  Bicyclic anti-VZV nucleosides: Thieno analogues retain full antiviral activity

  摘要：

  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.

  DOI：

  10.1016/s0960-894x(01)00471-1
• 作为产物：
  描述：

  1-十四炔 、 碘苷 在 copper(l) iodide 、 四(三苯基膦)钯 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以60%的产率得到5-tetradecynyl-2'-deoxyuridine
  参考文献：
  名称：

  Potent and Selective Inhibition of Varicella-Zoster Virus (VZV) by Nucleoside Analogues with an Unusual Bicyclic Base

  摘要：

  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.

  DOI：

  10.1021/jm990346o

文献信息

• [EN] ANTI-VIRAL PYRIMIDINE NUCLEOSIDE ANALOGUES<br/>[FR] ANALOGUES DE NUCLEOSIDES DE PYRIMIDINE ANTIVIRAUX
  申请人：UNIV CARDIFF

  公开号：WO1998049177A1

  公开（公告）日：1998-11-05

  A compound having formula (I), wherein R is selected from the group comprising C5 to C20 alkyl, C5 to C20 cycloalkyl, halogens, aryl and alkylaryl; R' is selected from the group comprising hydrogen, alkyl, cycloalkyl, halogens, amino, alkylamino, dialkylamino, nitro, cyano, alkyoxy, aryloxy, thiol, alkylthiol, arythiol, alkyl; R'' is selected from the group comprising hydrogen, alkyl, cycloalkyl, halogens, alkyloxy, aryloxy and aryl; Q is selected from the group comprising O, S and CY2, where Y may be the same or different and is selected from H, alkyl and halogens; X is selected from the group comprising O, NH, S, N- alkyl, (CH2)n where n is 1 to 10, and CY2 where Y may be the same or different and is selected from hydrogen, alkyl and halogens; Z is selected from the group comprising O, S, NH, and N alkyl; U'' is H and U' is selected from H and CH2T, or U' and U'' are joined so as to form a ring moiety including Q wherein U'-U'' together is respectively selected from the group comprising -CTH-CT'T''- and -CT=CT- and -CT'=CT'-, so as to provide ring moieties selected from the group comprising formula (II) and (III) wherein T is selected from the group comprising OH, H, halogens, O-alkyl, O-acyl, O-aryl, CN, NH2 and N3; T' is selected from the group comprising H and halogens and where more than one T' is present they may be the same or different; T'' is selected from the group comprising H and halogens, and W is selected from the group comprising H, a phosphate group and a pharmacologically acceptable salt, derivative or prodrug thereof shows potent anti-viral activity against, for example, varicella zoster virus and cytomegalovirus.

  化合物的化学式为（I），其中R选择自C5到C20烷基，C5到C20环烷基，卤素，芳基和烷基芳基的群体；R'选择自氢，烷基，环烷基，卤素，氨基，烷基氨基，双烷基氨基，硝基，氰基，烷氧基，芳氧基，硫醇，烷硫醇，芳硫醇，烷基；R''选择自氢，烷基，环烷基，卤素，烷氧基，芳氧基和芳基；Q选择自O，S和CY2的群体，其中Y可以相同或不同，选择自氢，烷基和卤素；X选择自O，NH，S，N-烷基，（CH2）n，其中n为1至10，和CY2，其中Y可以相同或不同，选择自氢，烷基和卤素；Z选择自O，S，NH和N烷基；U''为H，U'选择自H和CH2T，或U'和U''结合形成包括Q的环基，其中U'-U''分别选择自-CTH-CT'T''-和-CT=CT-和-CT'=CT'-，从而提供从化学式（II）和（III）中选择的环基，其中T选择自OH，H，卤素，O-烷基，O-酰基，O-芳基，CN，NH2和N3；T'选择自H和卤素，当存在多个T'时，它们可以相同或不同；T''选择自H和卤素，W选择自H，磷酸盐基团和药理学上可接受的盐，衍生物或前药，表现出强大的抗病毒活性，例如对带状疱疹病毒和巨细胞病毒。
• 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.
• ANTI-VIRAL PYRIMIDINE NUCLEOSIDE ANALOGUES
  申请人：University College Cardiff Consultants Limited

  公开号：EP0980377A1

  公开（公告）日：2000-02-23
• US6573247B1
  申请人：——

  公开号：US6573247B1

  公开（公告）日：2003-06-03
• 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.