3-{2-(methylsulfanyl)-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-4-yl}-8-oxa-3-azabicyclo[3.2.1]octane | 1233339-95-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 3-{2-(methylsulfanyl)-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-4-yl}-8-oxa-3-azabicyclo[3.2.1]octane
• 英文别名: 3-(6-(1-(methylsulfonyl)cyclopropyl)-2-(methylthio)pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane；3-[2-methylsulfanyl-6-(1-methylsulfonylcyclopropyl)pyrimidin-4-yl]-8-oxa-3-azabicyclo[3.2.1]octane
• CAS: 1233339-95-1
• 化学式: C₁₅H₂₁N₃O₃S₂
• 分子量: 355.482
• InChiKey: RAXDTPCOCHWISX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  106
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  吲哚-4-硼酸 、 3-{2-(methylsulfanyl)-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-4-yl}-8-oxa-3-azabicyclo[3.2.1]octane 在 四(三苯基膦)钯 、 噻吩-2-甲酸亚铜(I) 氮 、 desired product 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 以to afford the title compound (65 mg, 36%)的产率得到4-{4-[1-(methylsulfonyl)cyclopropyl]-6-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)pyrimidin-2-yl}-1H-indole
  参考文献：
  名称：

  CHEMICAL COMPOUNDS 610

  摘要：

  提供了式(I)的嘧啶基吲哚化合物或其药学上可接受的盐，其制备过程，包含它们的制药组合物以及它们在治疗中的使用。

  公开号：

  US20110053923A1
• 作为产物：
  描述：

  methyl [6-chloro-2-(methylsulfanyl)pyrimidin-4-yl](methylsulfonyl)acetate 在 四丁基溴化铵 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 90.0h， 生成 3-{2-(methylsulfanyl)-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-4-yl}-8-oxa-3-azabicyclo[3.2.1]octane
  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

文献信息

• [EN] PYRIMIDINE INDOLE DERIVATIVES FOR TREATING CANCER<br/>[FR] DÉRIVÉS DE PYRIMIDINE ET D'INDOLE POUR LE TRAITEMENT DU CANCER
  申请人：ASTRAZENECA AB

  公开号：WO2010073034A1

  公开（公告）日：2010-07-01

  There is provided pyrimidinyl indole compounds of Formula (I), or pharmaceutically acceptable salts thereof, processes for their preparation, pharmaceutical compositions containing them and their use in therapy, particularly for treating cancer.

  提供了式（I）的嘧啶基吲哚化合物，或其药用盐，其制备方法，含有它们的药物组合物以及它们在治疗中的应用，特别是用于治疗癌症。
• PYRIMIDINE INDOLE DERIVATIVES FOR TREATING CANCER
  申请人：AstraZeneca AB

  公开号：EP2379530A1

  公开（公告）日：2011-10-26