methyl [6-chloro-2-(methylsulfanyl)pyrimidin-4-yl](methylsulfonyl)acetate | 1426154-32-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: methyl [6-chloro-2-(methylsulfanyl)pyrimidin-4-yl](methylsulfonyl)acetate
• 英文别名: methyl 2-[6-chloro-2-(methylthio)pyrimidin-4-yl]-2-(methylsulfonyl)acetate；Methyl 2-(6-chloro-2-methylsulfanylpyrimidin-4-yl)-2-methylsulfonylacetate；methyl 2-(6-chloro-2-methylsulfanylpyrimidin-4-yl)-2-methylsulfonylacetate
• CAS: 1426154-32-6
• 化学式: C₉H₁₁ClN₂O₄S₂
• 分子量: 310.782
• InChiKey: LYHUNOIVCKLAPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  120
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl [6-chloro-2-(methylsulfanyl)pyrimidin-4-yl](methylsulfonyl)acetate 在 sodium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 4-(6-(methylsulfonylmethyl)-2-(methylthio)pyrimidin-4-yl)morpholine
  参考文献：
  名称：

  Expedient synthesis of biologically important sulfonylmethyl pyrimidines

  摘要：

  Two novel synthetic strategies that allow rapid diversification of the sulfone moiety in sulfonylmethyl pyrimidines, a class of compounds with a wide range of biological activity, which are of interest in a wide variety of drug discovery programmes, are described. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2014.04.111
• 作为产物：
  描述：

  4,6-二氯-二甲硫基嘧啶 、 甲磺酰乙酸甲酯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以58%的产率得到methyl [6-chloro-2-(methylsulfanyl)pyrimidin-4-yl](methylsulfonyl)acetate
  参考文献：
  名称：

  Discovery of 4-{4-[(3R)-3-Methylmorpholin-4-yl]-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-2-yl}-1H-indole (AZ20): A Potent and Selective Inhibitor of ATR Protein Kinase with Monotherapy in Vivo Antitumor Activity

  摘要：

  ATR is an attractive new anticancer drug target whose inhibitors have potential as chemo- or radiation sensitizers or as monotherapy in tumors addicted to particular DNA-repair pathways. We describe the discovery and synthesis of a series of sulfonylmorpholinopyrimidines that show potent and selective ATR inhibition. Optimization from a high quality screening hit within tight SAR space led to compound 6 (AZ20) which inhibits ATR immunoprecipitated from HeLa nuclear extracts with an IC50 of 5 nM and ATR mediated phosphorylation of Chk1 in HT29 colorectal adenocarcinoma tumor cells with an IC50 of 50 nM. Compound 6 potently inhibits the growth of LoVo colorectal adenocarcinoma tumor cells in vitro and has high free exposure in mouse following moderate oral doses. At well tolerated doses 6 leads to significant growth inhibition of LoVo xenografts grown in nude mice. Compound 6 is a useful compound to explore ATR pharmacology in vivo.

  DOI：

  10.1021/jm301859s