5-(4-trifluoromethylphenylethynyl)-1-(2,3,5-tri-hydroxy-β-D-ribofuranosyl)-1H-[1,2,4]triazole-3-carboxylic acid amide | 1106736-03-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 三唑核糖核苷和核糖核苷酸
• 英文名称: 5-(4-trifluoromethylphenylethynyl)-1-(2,3,5-tri-hydroxy-β-D-ribofuranosyl)-1H-[1,2,4]triazole-3-carboxylic acid amide
• 英文别名: 5-(4-trifluoromethylphenylethynyl)-1-(β-D-ribofuranosyl)-1H-[1,2,4]triazole-3-carboxylic acid amide；1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[2-[4-(trifluoromethyl)phenyl]ethynyl]-1,2,4-triazole-3-carboxamide
• CAS: 1106736-03-1
• 化学式: C₁₇H₁₅F₃N₄O₅
• 分子量: 412.325
• InChiKey: UKZFYWSWUCVKSR-XNIJJKJLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  144
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  5-(4-trifluoromethylphenylethynyl)-1-(2,3,5-tri-hydroxy-β-D-ribofuranosyl)-1H-[1,2,4]triazole-3-carboxylic acid amide 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 以98.5%的产率得到1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[2-[4-(trifluoromethyl)phenyl]ethyl]-1,2,4-triazole-3-carboxamide
  参考文献：
  名称：

  Discovery of Novel Arylethynyltriazole Ribonucleosides with Selective and Effective Antiviral and Antiproliferative Activity

  摘要：

  Novel ethynyltriazole ribonucleosides were synthesized using a simple and efficient two-step procedure involving Sonogashira coupling and subsequent ammonolysis. Compounds 2f and 3o inhibited hepatitis C virus (HCV) replication efficiently, whereas compound 3f demonstrated potent apoptosis-induced antiproliferative activity against pancreatic cancer MiaPaCa-2 cells both in vitro and in vivo. Most interestingly, the notable selective antiviral and antiproliferative activities were achieved respectively for 2f and 3f by modulating the ribose sugar moiety into deprotected and protected forms while retaining a similar trifluoromethylphenylethynyltriazole as the nucleobase. Preliminary structure-activity relationship study revealed that not only the ribose moiety but also the CF3 group at the p-position of the phenyl ring and the rigid triple bond functionality contributed critically to the observed antiviral activity of 2f against HCV and antiproliferative activity of 3f against pancreatic cancer. These two compounds constitute therefore promising leads in the search for new antiviral and anticancer candidates.

  DOI：

  10.1021/jm800927r
• 作为产物：
  描述：

  methyl 5-(4-trifluoromethylphenylethynyl)-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-[1,2,4]triazole-3-carboxylate 在 氨 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以73%的产率得到5-(4-trifluoromethylphenylethynyl)-1-(2,3,5-tri-hydroxy-β-D-ribofuranosyl)-1H-[1,2,4]triazole-3-carboxylic acid amide
  参考文献：
  名称：

  Novel triazole nucleoside derivatives, their preparation and their application in therapeutics

  摘要：

  本发明涉及一种新的化合物，其化学式为(I)，可以是自由碱或与酸形成的加成盐。本发明还涉及制备化合物(I)的方法，包括含有它们的组合物以及它们在治疗学中的应用，特别是在癌症治疗中的应用。

  公开号：

  EP2113508A1

文献信息

• Novel triazole nucleoside derivatives, their preparation and their application in therapeutics
  申请人：INSERM (Institut National de la Santé et de la Recherche Medicale)

  公开号：EP2113508A1

  公开（公告）日：2009-11-04

  The present invention relates to novel compound of formula (I): in the form of a free base or of an addition salt with an acid. The invention also relates to process of preparation of compounds of formula (I), to composition comprising them and to their application in therapeutics and in particular in cancers.

  本发明涉及一种新的化合物，其化学式为(I)，可以是自由碱或与酸形成的加成盐。本发明还涉及制备化合物(I)的方法，包括含有它们的组合物以及它们在治疗学中的应用，特别是在癌症治疗中的应用。
• [EN] TRIAZOLE DERIVATIVES AS VIRAL REPLICATION INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS DE RÉPLICATION VIRALE
  申请人：UNIV LEUVEN KATH

  公开号：WO2009015446A3

  公开（公告）日：2009-03-19
• Discovery of Novel Arylethynyltriazole Ribonucleosides with Selective and Effective Antiviral and Antiproliferative Activity
  作者：Jinqiao Wan、Yi Xia、Yang Liu、Menghua Wang、Palma Rocchi、Jianhua Yao、Fanqi Qu、Johan Neyts、Juan L. Iovanna、Ling Peng

  DOI：10.1021/jm800927r

  日期：2009.2.26

  Novel ethynyltriazole ribonucleosides were synthesized using a simple and efficient two-step procedure involving Sonogashira coupling and subsequent ammonolysis. Compounds 2f and 3o inhibited hepatitis C virus (HCV) replication efficiently, whereas compound 3f demonstrated potent apoptosis-induced antiproliferative activity against pancreatic cancer MiaPaCa-2 cells both in vitro and in vivo. Most interestingly, the notable selective antiviral and antiproliferative activities were achieved respectively for 2f and 3f by modulating the ribose sugar moiety into deprotected and protected forms while retaining a similar trifluoromethylphenylethynyltriazole as the nucleobase. Preliminary structure-activity relationship study revealed that not only the ribose moiety but also the CF3 group at the p-position of the phenyl ring and the rigid triple bond functionality contributed critically to the observed antiviral activity of 2f against HCV and antiproliferative activity of 3f against pancreatic cancer. These two compounds constitute therefore promising leads in the search for new antiviral and anticancer candidates.