tert-butyl 4-((2-methoxyethyl)carbamoyl)piperidine-1-carboxylate | 757949-34-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-((2-methoxyethyl)carbamoyl)piperidine-1-carboxylate
• 英文别名: Tert-butyl 4-[(2-methoxyethyl)carbamoyl]piperidine-1-carboxylate；tert-butyl 4-(2-methoxyethylcarbamoyl)piperidine-1-carboxylate
• CAS: 757949-34-1
• 化学式: C₁₄H₂₆N₂O₄
• 分子量: 286.371
• InChiKey: AYWYHJUDDBCCQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-((2-methoxyethyl)carbamoyl)piperidine-1-carboxylate 在 溶剂黄146 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 (S)-tert-butyl 5-amino-4-(4-((4-((4-((2-methoxyethyl)carbamoyl)piperidin-1-yl)methyl)benzyl)oxy)-1-oxoisoindolin-2-yl)-5-oxopentanoate
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS FOR TARGETED DEGRADATION OF PROTEINS IN A PLANT CELL
  [FR] COMPOSITIONS ET PROCÉDÉS DE DÉGRADATION CIBLÉE DE PROTÉINES DANS UNE CELLULE VÉGÉTALE

  摘要：

  Compounds, compositions, and methods for controlling the level of a target protein in a cell are described. Compounds of the disclosure include those having according to the formula PTM-L-LTM, wherein PTM is a targeting moiety that binds the target protein, L is a covalent bond or linker moiety, and LTM is a ubiquitin ligase binding moiety that binds a plant ubiquitin ligase. Additionally novel cereblon binding moieties are provided that may be used as molecular glues or in bifunctional compounds to target proteins in plants and mammals.

  公开号：

  WO2023034411A1
• 作为产物：
  描述：

  1-Boc-4-哌啶甲酸 、 2-甲氧基乙胺 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 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 tert-butyl 4-((2-methoxyethyl)carbamoyl)piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of Potent, Orally Bioavailable, Small-Molecule Inhibitors of WNT Signaling from a Cell-Based Pathway Screen

  摘要：

  WNT signaling is frequently deregulated in malignancy, particularly in colon cancer, and plays a key role in the generation and maintenance of cancer stem cells. We report the discovery and optimization of a 3,4,5-trisubstituted pyridine 9 using a high-throughput cell-based reporter assay of WNT pathway activity. We demonstrate a twisted conformation about the pyridine-piperidine bond of 9 by small-molecule X-ray crystallography. Medicinal chemistry optimization to maintain this twisted conformation, cognisant of physicochemical properties likely to maintain good cell permeability, led to 74 (CCT251545), a potent small-molecule inhibitor of WNT signaling with good oral pharmacokinetics. We demonstrate inhibition of WNT pathway activity in a solid human tumor xenograft model with evidence for tumor growth inhibition following oral dosing. This work provides a successful example of hypothesis-driven medicinal chemistry optimization from a singleton hit against a cell-based pathway assay without knowledge of the biochemical target.

  DOI：

  10.1021/jm501436m

文献信息

• Discovery of Potent, Orally Bioavailable, Small-Molecule Inhibitors of WNT Signaling from a Cell-Based Pathway Screen
  作者：Aurélie Mallinger、Simon Crumpler、Mark Pichowicz、Dennis Waalboer、Mark Stubbs、Olajumoke Adeniji-Popoola、Bozena Wood、Elizabeth Smith、Ching Thai、Alan T. Henley、Katrin Georgi、William Court、Steve Hobbs、Gary Box、Maria-Jesus Ortiz-Ruiz、Melanie Valenti、Alexis De Haven Brandon、Robert TePoele、Birgitta Leuthner、Paul Workman、Wynne Aherne、Oliver Poeschke、Trevor Dale、Dirk Wienke、Christina Esdar、Felix Rohdich、Florence Raynaud、Paul A. Clarke、Suzanne A. Eccles、Frank Stieber、Kai Schiemann、Julian Blagg

  DOI：10.1021/jm501436m

  日期：2015.2.26

  WNT signaling is frequently deregulated in malignancy, particularly in colon cancer, and plays a key role in the generation and maintenance of cancer stem cells. We report the discovery and optimization of a 3,4,5-trisubstituted pyridine 9 using a high-throughput cell-based reporter assay of WNT pathway activity. We demonstrate a twisted conformation about the pyridine-piperidine bond of 9 by small-molecule X-ray crystallography. Medicinal chemistry optimization to maintain this twisted conformation, cognisant of physicochemical properties likely to maintain good cell permeability, led to 74 (CCT251545), a potent small-molecule inhibitor of WNT signaling with good oral pharmacokinetics. We demonstrate inhibition of WNT pathway activity in a solid human tumor xenograft model with evidence for tumor growth inhibition following oral dosing. This work provides a successful example of hypothesis-driven medicinal chemistry optimization from a singleton hit against a cell-based pathway assay without knowledge of the biochemical target.
• [EN] COMPOSITIONS AND METHODS FOR TARGETED DEGRADATION OF PROTEINS IN A PLANT CELL<br/>[FR] COMPOSITIONS ET PROCÉDÉS DE DÉGRADATION CIBLÉE DE PROTÉINES DANS UNE CELLULE VÉGÉTALE
  申请人：[en]OERTH BIO LLC

  公开号：WO2023034411A1

  公开（公告）日：2023-03-09

  Compounds, compositions, and methods for controlling the level of a target protein in a cell are described. Compounds of the disclosure include those having according to the formula PTM-L-LTM, wherein PTM is a targeting moiety that binds the target protein, L is a covalent bond or linker moiety, and LTM is a ubiquitin ligase binding moiety that binds a plant ubiquitin ligase. Additionally novel cereblon binding moieties are provided that may be used as molecular glues or in bifunctional compounds to target proteins in plants and mammals.