4-formyl-5-methyl-1H-pyrrole-2-carboxylic acid | 98279-54-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 4-formyl-5-methyl-1H-pyrrole-2-carboxylic acid
• 英文别名: 4-formyl-5-methyl-pyrrole-2-carboxylic acid；4-Formyl-5-methyl-pyrrol-2-carbonsaeure
• CAS: 98279-54-0
• 化学式: C₇H₇NO₃
• 分子量: 153.137
• InChiKey: RPCXVOMVGMIQHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  70.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-formyl-5-methyl-1H-pyrrole-2-carboxylic acid 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 (S)-tert-butyl 3-(3-formyl-2-methyl-5-(2-methyl-4-phenylpiperazine-1-carbonyl)-1H-pyrrol-1-yl) propylcarbamate
  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
• 作为产物：
  描述：

  methyl 4-formyl-5-methyl-1H-pyrrole-2-carboxylate 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以99%的产率得到4-formyl-5-methyl-1H-pyrrole-2-carboxylic acid
  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] PYRROLE mTORC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS PYRROLES DE MTORC ET LEURS UTILISATIONS
  申请人：NAVITOR PHARM INC

  公开号：WO2018089493A1

  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、其组合物以及使用这些化合物的方法。
• Treibs; Ott, Justus Liebigs Annalen der Chemie, 1958, vol. 615, p. 137,163
  作者：Treibs、Ott

  DOI：——

  日期：——
• Discovery of Small-Molecule Selective mTORC1 Inhibitors via Direct Inhibition of Glucose Transporters
  作者：Seong A. Kang、David J. O'Neill、Andreas W. Machl、Casey J. Lumpkin、Stephanie N. Galda、Shomit Sengupta、Sarah J. Mahoney、Jessica J. Howell、Lisa Molz、Seung Hahm、George P. Vlasuk、Eddine Saiah

  DOI：10.1016/j.chembiol.2019.05.009

  日期：2019.9

  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.