| 351523-11-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• CAS: 351523-11-0
• 化学式: C₂₇H₃₆N₂O₈
• 分子量: 516.591
• InChiKey: GQFSNRHEMJMBKX-SLBCUGJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.78
• 重原子数：
  37.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  110.24
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  在 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以42 mg的产率得到1-(2-O-benzyl-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
• 作为产物：
  描述：

  在 氢氧化钾 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 20.0h， 生成
  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

• Design, Synthesis and Enzymatic Activity of Highly Selective Human Mitochondrial Thymidine Kinase Inhibitors
  作者：Stefano Manfredini、Pier G Baraldi、Elisa Durini、Luca Porcu、Angela Angusti、Silvia Vertuani、Nicola Solaroli、Erik De Clercq、Anna Karlsson、Jan Balzarini

  DOI：10.1016/s0960-894x(01)00207-4

  日期：2001.5

  Highly selective arabinofuranosyl nucleosides, which inhibit the mitochondrial thymidine kinase (TK-2) without affecting the closely related herpes simplex virus type 1 thymidine kinase (HSV-1 TK), varicella-zoster virus thymidine kinase (VZV-TK), cytosolic thymidine kinase (TK-1) or the multifunctional Drosophila melanogaster deoxyribonucleoside kinase (Dm-dNK), have been obtained. SAR studies indicate a close relation between the length of the substituent at the 2' position of the arabinofuranosyl moiety and the inhibitory activity. (C) 2001 Elsevier Science Ltd. All rights reserved.