3′,5′-dideoxy-3′,5′-bis-S-[(ethoxycarbonyl)methylthio]thymidine | 1446526-90-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3′,5′-dideoxy-3′,5′-bis-S-[(ethoxycarbonyl)methylthio]thymidine
• CAS: 1446526-90-4
• 化学式: C₁₈H₂₆N₂O₇S₂
• 分子量: 446.546
• InChiKey: YMYIAHRLVYACSQ-HZSPNIEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.09
• 重原子数：
  29.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  116.69
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  3′,5′-dideoxy-3′,5′-bis-S-[(ethoxycarbonyl)methylthio]thymidine 在 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 以61%的产率得到3′,5′-dideoxy-3′,5′-bis-S-[(carboxymethyl)thio]thymidine
  参考文献：
  名称：

  3′-Oxo-, amino-, thio- and sulfone-acetic acid modified thymidines: Effect of increased acidity on ribonuclease A inhibition

  摘要：

  A family of 3'-functionalized thymidines carrying XCH2COOH (X = O, NH, S, SO2) groups has been designed as inhibitors of RNase A. This is because it is possible to manipulate the overall acidity of this new class of nucleic 'acids' by changing X from oxygen to the SO2 group in the series. It is also expected that the acyclic nature of the XCH2COOH group would provide enough flexibility to the -COOH group to have maximum interactions with the catalytic subsite P-1 of RNase A. As the -SO2CH2COOH substituted derivative showed better potency partially because of the increased acidity of the -COOH group, the inhibitory properties of both 5'-substituted and 3',5'-disubstituted sulfone acetic acid modified thymidines were investigated. Two -SO2CH2COOH groups were incorporated with the expectation of targeting two phosphate binding sites simultaneously. Thus, 3',5'-dideoxy-3',5'-bis-S-[(carboxymethyl)sulfonyl]thymidine emerged as the best inhibitor in this series with a K-i value of 25 +/- 2 mu M. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.047
• 作为产物：
  描述：

  溴乙酸乙酯 、 3',5'-dithiothymidine 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以70%的产率得到3′,5′-dideoxy-3′,5′-bis-S-[(ethoxycarbonyl)methylthio]thymidine
  参考文献：
  名称：

  3′-Oxo-, amino-, thio- and sulfone-acetic acid modified thymidines: Effect of increased acidity on ribonuclease A inhibition

  摘要：

  A family of 3'-functionalized thymidines carrying XCH2COOH (X = O, NH, S, SO2) groups has been designed as inhibitors of RNase A. This is because it is possible to manipulate the overall acidity of this new class of nucleic 'acids' by changing X from oxygen to the SO2 group in the series. It is also expected that the acyclic nature of the XCH2COOH group would provide enough flexibility to the -COOH group to have maximum interactions with the catalytic subsite P-1 of RNase A. As the -SO2CH2COOH substituted derivative showed better potency partially because of the increased acidity of the -COOH group, the inhibitory properties of both 5'-substituted and 3',5'-disubstituted sulfone acetic acid modified thymidines were investigated. Two -SO2CH2COOH groups were incorporated with the expectation of targeting two phosphate binding sites simultaneously. Thus, 3',5'-dideoxy-3',5'-bis-S-[(carboxymethyl)sulfonyl]thymidine emerged as the best inhibitor in this series with a K-i value of 25 +/- 2 mu M. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.047