1-(2-deoxy-β-D-ribofuranosyl)-5-(2-iodoethynyl)uracil

• 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: 1-(2-deoxy-β-D-ribofuranosyl)-5-(2-iodoethynyl)uracil
• 英文别名: 5-(2-iodoethynyl)-2'-deoxyuridine；5-(2-iodoethynyl-2'-deoxyuridine；1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(2-iodoethynyl)pyrimidine-2,4-dione
• 化学式: C₁₁H₁₁IN₂O₅
• 分子量: 378.123
• InChiKey: VYTNCNUXXROEBU-DJLDLDEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 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

• 作为产物：
  描述：

  碘苷 在 copper(l) iodide 、 bis(triphenylphosphine)palladium(II)-chloride N-碘代丁二酰亚胺 、 silver nitrate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.5h， 生成 1-(2-deoxy-β-D-ribofuranosyl)-5-(2-iodoethynyl)uracil
  参考文献：
  名称：

  5-Alkynyl Analogs of Arabinouridine and 2‘-Deoxyuridine:  Cytostatic Activity against Herpes Simplex Virus and Varicella-Zoster Thymidine Kinase Gene-Transfected Cells

  摘要：

  A group of arabinouridines (TMSEAU, EAU, IEAU-TA) and 2'-deoxyuridines (TMSEDU, EDU, IEDU) having a variety of substituents at the uracil C-5 position (trimethylsilylethynyl, TMSE; ethynyl, E; or iodoethynyl, IE), and the sugar C-2' position (2'-arabino OH in arabinouridine, AU; or 2'-deoxyribo H in 2'-deoxyuridine, DU) were prepared to acquire antiviral structure-activity relationships. A broad-spectrum viral panel screen showed that these 5-alkynylarabino/deoxy-uridines exhibit moderate anti-HSV-1 activity, with no difference in potency between arabinouridines and 2'-deoxyuridines. The 2'-deoxyuridines TMSEDU, EDU, and IEDU, unlike the arabinouridines, exhibited potent antiviral activity against cytomegalovirus, but they were also highly cytostatic. The abilities of the 5-alkynylarabino/deoxy-uridines to inhibit nontransfected (wild-type or thymidine kinase-deficient, tk(-)) and viral gene transfected (HSV-1, HSV-2, or VZV thymidine kinase-positive, tk(+)) FM3A and OST (osteosarcoma) cells were determined. This group of 5-alkynylarabino/deoxy-uridines showed an enhanced ability to inhibit cells transfected with a viral thymidine kinase gene (HSV-1tk(+), HSV-2tk(+), VZVtk(+)) relative to wild-type or thymidine kinase-deficient (tk(-)) cells.

  DOI：

  10.1021/jm0701472

文献信息

• Uridine derivatives as antiviral drugs against a flaviviridae, especially HCV
  申请人：INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

  公开号：EP1674104A1

  公开（公告）日：2006-06-28

  The invention relates to the use of an uridine derivative of formula (I): wherein R1 represents monohalogenated alkynyl or dihalogenated alkenyl; R2 is chosen from among hydrogen, hydroxyl, -O-alkyl, -O-CO-alkyl and halogen; R3 is chosen from among hydrogen, hydroxyl, -O-alkyl, -O-CO-alkyl, halogen, -SH, -S-alkyl and N3; and R4 is chosen from among hydroxyl, -O-alkyl, -O-CO-alkyl, -O-phosphate, -O-diphosphate, -O-triphosphate and -O-phosphonate, as well as its possible tautomers, its possible pharmaceutically acceptable addition salts with an acid or a base, and its N-oxide forms, for the preparation of a drug having antiviral activity against a Flaviviridae.

  本发明涉及使用具有以下式（I）的尿苷衍生物： 其中 R1代表单卤代炔基或双卤代烯基； R2选择自氢、羟基、-O-烷基、-O-CO-烷基和卤素之一； R3选择自氢、羟基、-O-烷基、-O-CO-烷基、卤素、-SH、-S-烷基和N3之一； R4选择自羟基、-O-烷基、-O-CO-烷基、-O-磷酸酯、-O-二磷酸酯、-O-三磷酸酯和-O-膦酸酯之一， 以及其可能的互变异构体、其可能与酸或碱形成的药学上可接受的加合盐，以及其N-氧化物形式， 用于制备具有抗黄病毒活性的药物。
• Uridine Derivatives as Antiviral Drugs Against a Flaviviridae, Especially Hcv
  申请人：Aucagne Vincent

  公开号：US20090004137A1

  公开（公告）日：2009-01-01

  The invention relates to the use of an uridine derivative of formula (I); wherein —R 1 represents monohalogenated alkynyl or dihalogenated alkenyl; —R 2 is chosen from among hydrogen, hydroxyl, O-alkyl, O—CO alkyl and halogen; —R 3 is chosen from among hydrogen, hydroxyl, O-alkyl, O—CO alkyl, halogen, SH, S-alkyl and N 3 ; and —R 4 is chosen from among hydroxyl, O-alkyl, O—CO alkyl, O-phosphate, O-diphosphate, O-triphosphate and O phosphonate, as well as its possible tautomers, its possible pharmaceutically acceptable addition salts with an acid or a base, and its N-oxide forms, for the preparation of a drug having antiviral activity against a Flaviviridae.

  本发明涉及使用式（I）的尿嘧啶衍生物，其中—R1代表单卤代炔基或双卤代烯基；—R2选择自氢、羟基、O-烷基、O—CO烷基和卤素；—R3选择自氢、羟基、O-烷基、O—CO烷基、卤素、SH、S-烷基和N3；以及—R4选择自羟基、O-烷基、O—CO烷基、O-磷酸酯、O-二磷酸酯、O-三磷酸酯和O-膦酸酯，以及其可能的互变异构体、其可能的与酸或碱的药学上可接受的加盐物和其N-氧化物形式，用于制备具有抗Flaviviridae病毒活性的药物。
• Synthesis of 5-haloethynyl- and 5-(1,2-dihalo)vinyluracil nucleosides: Antiviral activity and cellular toxicity
  作者：Vanessa Escuret、Vincent Aucagne、Nicolas Joubert、David Durantel、Kimberly L. Rapp、Raymond F. Schinazi、Fabien Zoulim、Luigi A. Agrofoglio

  DOI：10.1016/j.bmc.2005.06.021

  日期：2005.11

  In this article, we report the synthesis of hitherto unknown 5-haloethynyl and 5-(1,2-dihalo)vinyluracil nucleosides in the 2'-deoxy, 3'-deoxy- and ribosyl series, and we discuss their in vitro anti-HIV and anti-HCV activities and cellular toxicitites. As a result, on the basis of their selectivity index (SI) obtained with the HCV replicon system, but also on their cytotoxicity on peripheral blood mononuclear, CEM and VERO cell lines, the best compounds were the 5-bromoethynyluridine (SI = 3.2) and the 5-(1-chloro-2-iodo)vinyluridine (SI > 2.8). (c) 2005 Elsevier Ltd. All rights reserved.
• URIDINE DERIVATIVES AS ANTIVIRAL DRUGS AGAINST A FLAVIVIRIDAE, ESPECIALLY HCV
  申请人：INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

  公开号：EP1827457A1

  公开（公告）日：2007-09-05
• [EN] URIDINE DERIVATIVES AS ANTIVIRAL DRUGS AGAINST A FLAVIVIRIDAE, ESPECIALLY HCV<br/>[FR] DERIVES D'URIDINE UTILISES COMME MEDICAMENTS ANTIVIRAUX CONTRE UN VIRUS DE LA FAMILLE DES FLAVIVIRIDAE, EN PARTICULIER LE VHC
  申请人：INST NAT SANTE RECH MED

  公开号：WO2006067606A1

  公开（公告）日：2006-06-29

  [EN] The invention relates to the use of an uridine derivative of formula (I) : wherein - R¹ represents monohalogenated alkynyl or dihalogenated alkenyl; - R² is chosen from among hydrogen, hydroxyl, O-alkyl, O-CO alkyl and halogen; - R³ is chosen from among hydrogen, hydroxyl, O-alkyl, O-CO alkyl, halogen, SH, S-alkyl and N³; and - R⁴ is chosen from among hydroxyl, O-alkyl, O-CO alkyl, O-phosphate, O-diphosphate, O-triphosphate and O phosphonate, as well as its possible tautomers, its possible pharmaceutically acceptable addition salts with an acid or a base, and its N-oxide forms, for the preparation of a drug having antiviral activity against a Flaviviridae.
  [FR] L'invention concerne l'utilisation d'un dérivé d'uridine de formule (I), ainsi que de ses tautomères éventuels, ses sels d'addition d'acides pharmaceutiquement acceptables éventuels avec un acide ou une base, ainsi que ses formes N-oxyde, pour préparer un médicament possédant une activité antivirale contre un virus de la famille des Flaviviridae. Dans ladite formule (I), R¹ représente un groupe alcynyle monohalogéné ou alcényle dihalogéné, R² est choisi parmi un atome d'hydrogène, un groupe hydroxyle, un groupe -O-alkyle, un groupe -O-CO-alkyle et un atome d'halogène, R³ est choisi parmi un atome d'hydrogène, un groupe hydroxyle, un groupe -O-alkyle, un groupe -O-CO-alkyle, un atome d'halogène, un groupe -SH, un groupe -S-alkyle et N³ et R⁴ est choisi parmi les groupes hydroxyle, -O-alkyle, -O-CO-alkyle, -O-phosphate, -O-diphosphate, -O-triphosphate et -O-phosphonate.