2-[4-(5-{[4-(2-cyanophenyl)piperazin-1-yl]methyl}-2,4-dimethylbenzoyl)piperazin-1-yl]benzene-1-sulfonamide | 2226614-88-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-[4-(5-{[4-(2-cyanophenyl)piperazin-1-yl]methyl}-2,4-dimethylbenzoyl)piperazin-1-yl]benzene-1-sulfonamide
• 英文别名: 2-[4-[5-[[4-(2-Cyanophenyl)piperazin-1-yl]methyl]-2,4-dimethylbenzoyl]piperazin-1-yl]benzenesulfonamide
• CAS: 2226614-88-4
• 化学式: C₃₁H₃₆N₆O₃S
• 分子量: 572.731
• InChiKey: BREWSTIKWAQLCH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  41
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  122
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-(2-苯甲腈)哌嗪 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 2-[4-(5-{[4-(2-cyanophenyl)piperazin-1-yl]methyl}-2,4-dimethylbenzoyl)piperazin-1-yl]benzene-1-sulfonamide
  参考文献：
  名称：

  Discovery of Small-Molecule Selective mTORC1 Inhibitors via Direct Inhibition of Glucose Transporters

  摘要：

  The mechanistic target of rapamycin (mTOR) is a central regulator of cellular metabolic processes. Dysregulation of this kinase complex can result in a variety of human diseases. Rapamycin and its analogs target mTORC1 directly; however, chronic treatment in certain cell types and in vivo results in the inhibition of both mTORC1 and mTORC2. We have developed a high-throughput cell-based screen for the detection of phosphorylated forms of the mTORC1 (4E-BP1, S6K1) and mTORC2 (Akt) substrates and have identified and characterized a chemical scaffold that demonstrates a profile consistent with the selective inhibition of mTORC1. Stable isotope labeling of amino acids in cell culture-based proteomic target identification revealed that class I glucose transporters were the primary target for these compounds yielding potent inhibition of glucose uptake and, as a result, selective inhibition of mTORC1. The link between the glucose uptake and selective mTORC1 inhibition are discussed in the context of a yet-to-be discovered glucose sensor.

  DOI：

  10.1016/j.chembiol.2019.05.009

文献信息

• [EN] PHENYL mTORC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE MTORC PHÉNYLE ET LEURS UTILISATIONS
  申请人：NAVITOR PHARM INC

  公开号：WO2018089433A1

  公开（公告）日：2018-05-17

  The present invention provides compounds, compositions thereof, and methods of using the same.

  本发明提供了化合物、其组合物以及使用相同的方法。