1-(2-(N-nonylcarboxamido)-2-deoxy-β-D-arabinofuranosyl)thymine

• 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-(N-nonylcarboxamido)-2-deoxy-β-D-arabinofuranosyl)thymine
• 英文别名: 1-(2''-N-nonylcarboxamido-2''-deoxy-beta-D-arabinofuranosyl)thymine；N-[(2R,3S,4S,5R)-4-hydroxy-5-(hydroxymethyl)-2-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]decanamide
• 化学式: C₂₀H₃₃N₃O₆
• 分子量: 411.499
• InChiKey: BNQBARJQAVAVPK-NOCIGQNYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  128
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3',5'-bis-O-tetrahydropyranyl-araU 在 ammonium hydroxide 、 氟化铵 、 sodium hydride 、 对甲苯磺酸 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 87.0h， 生成 1-(2-(N-nonylcarboxamido)-2-deoxy-β-D-arabinofuranosyl)thymine
  参考文献：
  名称：

  Novel selective human mitochondrial kinase inhibitors: Design, synthesis and enzymatic activity

  摘要：

  Selective and effective TK2 inhibitors can be obtained by introduction of bulky lipophilic chains (acyl or alkyl entities) at the 2' position of araT and BVaraU, nucleoside analogues naturally endowed with a low TK2 affinity. These derivatives showed a competitive inhibitory activity against TK2 in micromolar range. BVaraU nucleoside analogues, modified on the 2'-O-acyl chain with a terminal N-Boc amino-group, conserved or increased the inhibitory activity against TK2 (71 and 7m IC50: 6.4 and 3.8 mu M, respectively). The substitution of an ester for a carboxamide moiety at the 2' position of araT afforded a consistent reduction of the inhibitory activity (25, IC50: 480 mu M). On the contrary, modifications at 2'-OH position of araC and araG, have provided inactive derivatives against TK2 and dGK, respectively. The biological activity of a representative compound, 2'-O-decanoyl-BVaraU, was also investigated in normal human fibroblasts and was found to impair mitochondrial function due to TK2 inhibition. (c) 2007 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2007.01.049

文献信息

• Novel selective human mitochondrial kinase inhibitors: Design, synthesis and enzymatic activity
  作者：Nunzia Ciliberti、Stefano Manfredini、Angela Angusti、Elisa Durini、Nicola Solaroli、Silvia Vertuani、Lisa Buzzoni、Maria Cruz Bonache、Efrat Ben-Shalom、Anna Karlsson、Ann Saada、Jan Balzarini

  DOI：10.1016/j.bmc.2007.01.049

  日期：2007.4

  Selective and effective TK2 inhibitors can be obtained by introduction of bulky lipophilic chains (acyl or alkyl entities) at the 2' position of araT and BVaraU, nucleoside analogues naturally endowed with a low TK2 affinity. These derivatives showed a competitive inhibitory activity against TK2 in micromolar range. BVaraU nucleoside analogues, modified on the 2'-O-acyl chain with a terminal N-Boc amino-group, conserved or increased the inhibitory activity against TK2 (71 and 7m IC50: 6.4 and 3.8 mu M, respectively). The substitution of an ester for a carboxamide moiety at the 2' position of araT afforded a consistent reduction of the inhibitory activity (25, IC50: 480 mu M). On the contrary, modifications at 2'-OH position of araC and araG, have provided inactive derivatives against TK2 and dGK, respectively. The biological activity of a representative compound, 2'-O-decanoyl-BVaraU, was also investigated in normal human fibroblasts and was found to impair mitochondrial function due to TK2 inhibition. (c) 2007 Published by Elsevier Ltd.