(2R,3R,4S,5R)-2-(7-amino-5-(benzylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol | 1260177-39-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2R,3R,4S,5R)-2-(7-amino-5-(benzylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
• 英文别名: 2-BnS-8-aza-adenosine；(2R,3R,4S,5R)-2-(7-amino-5-benzylsulfanyltriazolo[4,5-d]pyrimidin-3-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 1260177-39-6
• 化学式: C₁₆H₁₈N₆O₄S
• 分子量: 390.423
• InChiKey: IFOVGXCNMQIBPU-SDBHATRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  178
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-苄硫基-4,6-二氨基嘧啶 在 盐酸 、 platinum(IV) oxide 、 H₄N⁽¹⁺⁾*O₄S^(2-) 、 氢气 、 溶剂黄146 、 六甲基二硅氮烷 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 为溶剂， 140.0 ℃ 、101.33 kPa 条件下， 反应 24.5h， 生成 (2R,3R,4S,5R)-2-(7-amino-5-(benzylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
  参考文献：
  名称：

  Investigations into the Origin of the Molecular Recognition of Several Adenosine Deaminase Inhibitors

  摘要：

  Inhibitors of adenosine deaminase (ADA, EC 3 5 4 4) are potential therapeutic agents for the treatment of various health disorders Several highly potent inhibitors were previously identified, yet they exhibit unacceptable toxicities We performed a SAR study involving a series of C2 or C8 substituted purine-riboside analogues with a view to discover less potent inhibitors with a lesser toxicity We found that any substitution at C8 position of nebularine resulted in total loss of activity toward calf intestinal ADA However several 2-substituted-adenosine, 8-aza-adenosine, and nebularine analogues exhibited inhibitory activity Specifically, 2-Cl-purine riboside, 8-aza-2-thiohexyl adenosine, 2-thiohexyl adenosine, and 2-MeS-purine riboside were found to be competitive inhibitors of ADA with K-i values of 25, 22, 6, and 3 mu M, respectively We concluded that electronic parameters are not major recognition determinants of ADA but rather steric parameters A C2 substituent which fits ADA hydrophobic pocket and improves H-bonding with the enzyme makes a good inhibitor In addition, a gg rotamer about C4'-C5' bond is apparently an important recognition determinant

  DOI：

  10.1021/jm101286g

文献信息

• Investigations into the Origin of the Molecular Recognition of Several Adenosine Deaminase Inhibitors
  作者：Irina Gillerman、Bilha Fischer

  DOI：10.1021/jm101286g

  日期：2011.1.13

  Inhibitors of adenosine deaminase (ADA, EC 3 5 4 4) are potential therapeutic agents for the treatment of various health disorders Several highly potent inhibitors were previously identified, yet they exhibit unacceptable toxicities We performed a SAR study involving a series of C2 or C8 substituted purine-riboside analogues with a view to discover less potent inhibitors with a lesser toxicity We found that any substitution at C8 position of nebularine resulted in total loss of activity toward calf intestinal ADA However several 2-substituted-adenosine, 8-aza-adenosine, and nebularine analogues exhibited inhibitory activity Specifically, 2-Cl-purine riboside, 8-aza-2-thiohexyl adenosine, 2-thiohexyl adenosine, and 2-MeS-purine riboside were found to be competitive inhibitors of ADA with K-i values of 25, 22, 6, and 3 mu M, respectively We concluded that electronic parameters are not major recognition determinants of ADA but rather steric parameters A C2 substituent which fits ADA hydrophobic pocket and improves H-bonding with the enzyme makes a good inhibitor In addition, a gg rotamer about C4'-C5' bond is apparently an important recognition determinant