methyl 5-(4-fluorophenylethynyl)-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-[1,2,4]triazole-3-carboxylate | 1106735-95-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物
• 英文名称: methyl 5-(4-fluorophenylethynyl)-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-[1,2,4]triazole-3-carboxylate
• 英文别名: methyl 1-[(2R,3R,4R,5R)-3,4-diacetyloxy-5-(acetyloxymethyl)oxolan-2-yl]-5-[2-(4-fluorophenyl)ethynyl]-1,2,4-triazole-3-carboxylate
• CAS: 1106735-95-8
• 化学式: C₂₃H₂₂FN₃O₉
• 分子量: 503.441
• InChiKey: GJWQIFKZZMXKKZ-JWUVWSEFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  145
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  methyl 5-(4-fluorophenylethynyl)-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77%的产率得到1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[2-(4-fluorophenyl)ethynyl]-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：

  4-氟苯乙炔 、 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82%的产率得到methyl 5-(4-fluorophenylethynyl)-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

• [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
• [EN] NOVEL VIRAL REPLICATION INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS DE RÉPLICATION VIRALE
  申请人：UNIV LEUVEN KATH

  公开号：WO2009015446A2

  公开（公告）日：2009-02-05

  The present invention relates to novel compounds and to their use as a medicament, more in particular for the treatment or prevention of viral infections in mammals. The invention also relates to processes for the preparation of compounds according to the invention and to pharmaceutical compositions comprising them.