1-[3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-β-D-arabinofuranosyl]thymine | 161602-00-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-β-D-arabinofuranosyl]thymine
• 英文别名: 1-[(6aR,8R,9S,9aS)-9-hydroxy-2,2,4,4-tetra(propan-2-yl)-6a,8,9,9a-tetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl]-5-methylpyrimidine-2,4-dione
• CAS: 161602-00-2
• 化学式: C₂₂H₄₀N₂O₇Si₂
• 分子量: 500.74
• InChiKey: FXSUFWJWZYCZNU-RCLSDMTESA-N

物化性质

• 熔点：
  >250 °C (decomp)
• 密度：
  1.16±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.06
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-[3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-β-D-arabinofuranosyl]thymine 在 吡啶 、 氟化铵 、 Dowex H₊ form 50x2-100 作用下， 以 甲醇 为溶剂， 生成 2'-O-decanoyl-1-β-D-arabinofuranosylthymine
  参考文献：
  名称：

  Design, Synthesis and Enzymatic Activity of Highly Selective Human Mitochondrial Thymidine Kinase Inhibitors

  摘要：

  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.

  DOI：

  10.1016/s0960-894x(01)00207-4
• 作为产物：
  描述：

  1,3二氯-1,1,3,3-四异丙基二硅氧烷 、 1-β-D-阿拉伯呋喃糖苷胸腺嘧啶 在 吡啶 作用下， 生成 1-[3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-β-D-arabinofuranosyl]thymine
  参考文献：
  名称：

  Design, Synthesis and Enzymatic Activity of Highly Selective Human Mitochondrial Thymidine Kinase Inhibitors

  摘要：

  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.

  DOI：

  10.1016/s0960-894x(01)00207-4

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.
• 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.