ethyl 3-((tert-butyldimethylsilyl)oxy)benzyl(6-chloro-2-(methylthio)-5-nitropyrimidin-4-yl)carbamate | 1539304-14-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 3-((tert-butyldimethylsilyl)oxy)benzyl(6-chloro-2-(methylthio)-5-nitropyrimidin-4-yl)carbamate
• 英文别名: ethyl N-[[3-[tert-butyl(dimethyl)silyl]oxyphenyl]methyl]-N-(6-chloro-2-methylsulfanyl-5-nitropyrimidin-4-yl)carbamate
• CAS: 1539304-14-7
• 化学式: C₂₁H₂₉ClN₄O₅SSi
• 分子量: 513.09
• InChiKey: UJDAIYGUMWLTIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.31
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  136
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 3-((tert-butyldimethylsilyl)oxy)benzyl(6-chloro-2-(methylthio)-5-nitropyrimidin-4-yl)carbamate 在 ammonium hydroxide 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 36.0h， 生成 ethyl N-(6-amino-2-methylsulfonyl-5-nitropyrimidin-4-yl)-N-[[3-[tert-butyl(dimethyl)silyl]oxyphenyl]methyl]carbamate
  参考文献：
  名称：

  [EN] MACROCYCLIC PURINES FOR THE TREATMENT OF VIRAL INFECTIONS
  [FR] PURINES MACROCYCLIQUES DESTINÉES AU TRAITEMENT D'INFECTIONS VIRALES

  摘要：

  这项发明涉及具有式(I)的大环嘌呤衍生物，其制备方法，药物组合物以及它们在治疗病毒感染中的应用。

  公开号：

  WO2014009509A1
• 作为产物：
  描述：

  3-(tert-butyldimethylsilyloxy)benzyl alcohol 在 氯化亚砜 、 potassium carbonate 、 sodium iodide 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 21.0h， 生成 ethyl 3-((tert-butyldimethylsilyl)oxy)benzyl(6-chloro-2-(methylthio)-5-nitropyrimidin-4-yl)carbamate
  参考文献：
  名称：

  Potent and Selective Inhibitors of MTH1 Probe Its Role in Cancer Cell Survival

  摘要：

  Recent literature has claimed that inhibition of the enzyme MTH1 can eradicate cancer. MTH1 is one of the "housekeeping" enzymes that are responsible for hydrolyzing damaged nucleotides in cells and thus prevent them from being incorporated into DNA. We have developed orthogonal and chemically distinct tool compounds to those published in the literature to allow us to test the hypothesis that inhibition of MTH1 has wide applicability in the treatment of cancer. Here we present the work that led to the discovery of three structurally different series of MTH1 inhibitors with excellent potency, selectivity, and proven target engagement in cells. None of these compounds elicited the reported cellular phenotype, and additional siRNA and CRISPR experiments further support these observations. Critically, the difference between the responses of our highly selective inhibitors and published tool compounds suggests that the effect reported for the latter may be due to off-target cytotoxic effects. As a result, we conclude that the role of MTH1 in carcinogenesis and utility of its inhibition is yet to be established.

  DOI：

  10.1021/acs.jmedchem.5b01760