methyl 5-(cyclohexenylethynyl)-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-[1,2,4]triazole-3-carboxylate | 1123187-58-5

• 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: methyl 5-(cyclohexenylethynyl)-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-[1,2,4]triazole-3-carboxylate
• 英文别名: methyl 5-[2-(cyclohexen-1-yl)ethynyl]-1-[(2R,3R,4R,5R)-3,4-diacetyloxy-5-(acetyloxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxylate
• CAS: 1123187-58-5
• 化学式: C₂₃H₂₇N₃O₉
• 分子量: 489.482
• InChiKey: AYMIJBZDMANDOC-JWUVWSEFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  145
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  methyl 5-(cyclohexenylethynyl)-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86%的产率得到5-[2-(cyclohexen-1-yl)ethynyl]-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-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：

  1-乙炔基环己烷 、 5-bromo-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxylic acid methyl ester 在 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 0.5h， 以86%的产率得到methyl 5-(cyclohexenylethynyl)-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-[1,2,4]triazole-3-carboxylate
  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

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。
• NOVEL TRIAZOLE DERIVATIVES, THEIR PREPARATION AND THEIR APPLICATION IN THERAPEUTICS
  申请人：Inserm Transfert

  公开号：EP2279193A1

  公开（公告）日：2011-02-02
• US8563526B2
  申请人：——

  公开号：US8563526B2

  公开（公告）日：2013-10-22
• [EN] NOVEL TRIAZOLE DERIVATIVES, THEIR PREPARATION AND THEIR APPLICATION IN THERAPEUTICS<br/>[FR] NOUVEAUX DÉRIVÉS DE TRIAZOLE, LEUR PRÉPARATION ET LEUR APPLICATION EN THÉRAPEUTIQUE
  申请人：INSERM TRANSFERT

  公开号：WO2009133147A1

  公开（公告）日：2009-11-05

  The present invention relates to novel compounds of formula (A): 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 (A), to composition comprising them and to their application in therapeutics and in particular in cancers.