1-[3′,5′-bis-S-(methoxycarbonyl)methyl-2′-deoxy-3′,5′-dithio-β-d-threo-pentofuranosyl]thymine | 1446526-95-9

• 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: 1-[3′,5′-bis-S-(methoxycarbonyl)methyl-2′-deoxy-3′,5′-dithio-β-d-threo-pentofuranosyl]thymine
• 英文别名: methyl 2-[[(2R,3R,5R)-3-(2-methoxy-2-oxoethyl)sulfanyl-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methylsulfanyl]acetate
• CAS: 1446526-95-9
• 化学式: C₁₆H₂₂N₂O₇S₂
• 分子量: 418.492
• InChiKey: BGFUHKNMOIJWDE-IJLUTSLNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  162
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-[3′,5′-bis-S-(methoxycarbonyl)methyl-2′-deoxy-3′,5′-dithio-β-d-threo-pentofuranosyl]thymine 在 MMPP 作用下， 反应 8.0h， 以70%的产率得到1-[3′,5′-bis-S-(methoxycarbonyl)methyl-2′-deoxy-3′,5′-disulfonyl-β-d-threo-pentofuranosyl]thymine
  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：

  巯基乙酸甲酯 、 3',5'-二-氧-对甲苯磺酰基胸苷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 3.0h， 以76%的产率得到1-[3′,5′-bis-S-(methoxycarbonyl)methyl-2′-deoxy-3′,5′-dithio-β-d-threo-pentofuranosyl]thymine
  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

文献信息

• 3′-Oxo-, amino-, thio- and sulfone-acetic acid modified thymidines: Effect of increased acidity on ribonuclease A inhibition
  作者：Dhrubajyoti Datta、Anirban Samanta、Swagata Dasgupta、Tanmaya Pathak

  DOI：10.1016/j.bmc.2013.05.047

  日期：2013.8

  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.