3-(2'-deoxy-β-D-ribofuranosyl)-6-decyl-2,3-dihydrofuro[2,3-d]pyrimidin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃[2,3-d]嘧啶
• 英文名称: 3-(2'-deoxy-β-D-ribofuranosyl)-6-decyl-2,3-dihydrofuro[2,3-d]pyrimidin-2-one
• 英文别名: 6-decyl-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]furo[2,3-d]pyrimidin-2-one；6-decyl-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]furo[2,3-d]pyrimidin-2-one
• 化学式: C₂₁H₃₂N₂O₅
• 分子量: 392.495
• InChiKey: YDVGWQCQUBLRBT-IPMKNSEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  91.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-癸炔 在 palladium on activated charcoal 、 copper(l) iodide 、 四(三苯基膦)钯 氨 、 氢气 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、172.37 kPa 条件下， 反应 6.0h， 生成 3-(2'-deoxy-β-D-ribofuranosyl)-6-decyl-2,3-dihydrofuro[2,3-d]pyrimidin-2-one
  参考文献：
  名称：

  Synthesis and Antiviral Evaluation of 6-(Alkyl-heteroaryl)furo[2,3-d]pyrimidin-2(3H)-one Nucleosides and Analogues with Ethynyl, Ethenyl, and Ethyl Spacers at C6 of the Furopyrimidine Core

  摘要：

  Sonogashira coupling strategies were employed to synthesize new furo[2,3-d]pyrimidin-2(3H)-one (FuPyrm) 2'-deoxynucleoside analogues. Partial or complete reduction of ethyne-linked compounds afforded ethenyl-and ethyl-linked derivatives. Levels of inhibition of varicella-zoster virus (VZV), human cytomegalovirus (HCMV), a broad range of other DNA and RNA viruses, and several cancer cell lines were evaluated in cell cultures. The anti-VZV potency decreased with increasing rigidity of the side chain at C6 of the FuPyrm ring in the order dec-1-yn-1-yl < dec-1-en-1-yl < decan-1-yl. In contrast, compounds with a rigid ethynyl spacer between C6 of the FuPyrm ring and a 4-alkylphenyl moiety were more potent inhibitors of VZV than the corresponding derivatives with an ethyl spacer. Replacement of the phenyl moiety in 6-(4-alkylphenyl) derivatives with a pyridine ring (in either regioisomeric orientation) gave analogues with increased solubility in methanol but reduced anti-VZV potency, and replacement with a pyrimidine ring reduced the anti-VZV activity even further. The pyridine-ring-containing analogues were similar to 20-fold more potent inhibitors of VZV than acyclovir but were similar to 6-fold less potent than BVDU and similar to 60-fold weaker than the most active 6-(4-pentylphenyl) -substituted prototype.

  DOI：

  10.1021/jm070210n

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.
• 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：EP1280813A1

  公开（公告）日：2003-02-05
• Anti-Viral Pyrimidine Nucleoside Analogues
  申请人：University College Cardiff Consultants Limited

  公开号：US20140011764A1

  公开（公告）日：2014-01-09

  A compound of formula (I) wherein Ar can be one six-membered or two fused six-membered aromatic rings; R 8 and R 9 can be hydrogen, alkyl, cycloalkyl, halogen, amino, alkylamino, dialkylamino, nitro, cyano, alkyoxy, aryloxy, thiol, alkylthiol, arythiol, or aryl; Q can be O, S or CY 2 , where Y may be H, alkyl or halogen; X can be O, NH, S, N-alkyl, (CHR 2 ) m where m is 1 to 10, and CY 2 ; Z can be O, S, NH, or N-alkyl; U″ is H and U′ can be H or CH 2; wherein: T can be OH, H, halogen, O-alkyl, O-acyl, O-aryl, CN, NH 2 or N 3 ; T′ and T″ can be H or halogen; and W can be H or a phosphate group. Compounds show anti-viral activity, for example with respect to varicella zoster virus.
• US8551965B2
  申请人：——

  公开号：US8551965B2

  公开（公告）日：2013-10-08