4-[2-(1-Methylindol-5-yl)-6-(methylsulfonylmethyl)pyrimidin-4-yl]morpholine | 1382298-26-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-[2-(1-Methylindol-5-yl)-6-(methylsulfonylmethyl)pyrimidin-4-yl]morpholine
• CAS: 1382298-26-1
• 化学式: C₁₉H₂₂N₄O₃S
• 分子量: 386.475
• InChiKey: ZTTVDKACTJBDHD-UHFFFAOYSA-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：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  85.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6-(氯甲基)-2-(甲基硫代)嘧啶-4(3h)-酮 在 四(三苯基膦)钯 、 噻吩-2-甲酸亚铜(I) 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 20.75h， 生成 4-[2-(1-Methylindol-5-yl)-6-(methylsulfonylmethyl)pyrimidin-4-yl]morpholine
  参考文献：
  名称：

  Sulfonyl-morpholino-pyrimidines: SAR and development of a novel class of selective mTOR kinase inhibitor

  摘要：

  High throughput screening to identify inhibitors of the mTOR kinase revealed sulfonyl-morpholino-pyrimidine 1 as an attractive start point. The compound displayed good physicochemical properties and selectivity over related kinases such as PI3K alpha. Library preparation of related analogs allowed the establishment of additional SAR understanding and in particular the requirement for a key hydrogen bond donor motif at the 4-position of the phenyl ring in compounds such as indole 19. Isosteric replacement of the indole functionality led to the identification of urea compounds such as 32 that show good levels of mTOR inhibition in both enzyme and cellular assays. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.036

文献信息

• Sulfonyl-morpholino-pyrimidines: SAR and development of a novel class of selective mTOR kinase inhibitor
  作者：M. Raymond V. Finlay、David Buttar、Susan E. Critchlow、Allan P. Dishington、Shaun M. Fillery、Eric Fisher、Steve C. Glossop、Mark A. Graham、Trevor Johnson、Gillian M. Lamont、Simon Mutton、Paula Perkins、Kurt G. Pike、Anthony M. Slater.

  DOI：10.1016/j.bmcl.2012.04.036

  日期：2012.6

  High throughput screening to identify inhibitors of the mTOR kinase revealed sulfonyl-morpholino-pyrimidine 1 as an attractive start point. The compound displayed good physicochemical properties and selectivity over related kinases such as PI3K alpha. Library preparation of related analogs allowed the establishment of additional SAR understanding and in particular the requirement for a key hydrogen bond donor motif at the 4-position of the phenyl ring in compounds such as indole 19. Isosteric replacement of the indole functionality led to the identification of urea compounds such as 32 that show good levels of mTOR inhibition in both enzyme and cellular assays. (C) 2012 Elsevier Ltd. All rights reserved.