methyl 3-(4-(tert-butoxy)-4-oxobutoxy)benzoate | 1448189-94-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 3-(4-(tert-butoxy)-4-oxobutoxy)benzoate
• 英文别名: Methyl 3-(4-(tert-butoxy)-4-oxobutoxy)benzoate；methyl 3-[4-[(2-methylpropan-2-yl)oxy]-4-oxobutoxy]benzoate
• CAS: 1448189-94-3
• 化学式: C₁₆H₂₂O₅
• 分子量: 294.348
• InChiKey: DEXWTRPDYNTPAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-(4-(tert-butoxy)-4-oxobutoxy)benzoate 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 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 tert-butyl 4-(3-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidine-1-carbonyl)phenoxy)butanoate
  参考文献：
  名称：

  Compounds & Methods for the Enhanced Degradation of Targeted Proteins & Other Polypeptides by an E3 Ubiquitin Ligase

  摘要：

  本发明涉及双功能化合物，其作为靶向泛素化的调节剂具有实用性，特别是作为本发明的双功能化合物对各种被降解和/或受到抑制的多肽和其他蛋白质的抑制剂。具体而言，本发明涉及含有一端结合泛素连接酶的VHL配体，另一端结合靶蛋白的基团的化合物，使得靶蛋白靠近泛素连接酶以促使该蛋白的降解（和抑制）。本发明展示了与本发明化合物相关的广泛的药理活性范围，与靶向多肽的降解/抑制一致。

  公开号：

  US20140356322A1
• 作为产物：
  描述：

  3-羟基苯甲酸甲酯 、 4-溴丁酸叔丁酯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 以72%的产率得到methyl 3-(4-(tert-butoxy)-4-oxobutoxy)benzoate
  参考文献：
  名称：

  Compounds & Methods for the Enhanced Degradation of Targeted Proteins & Other Polypeptides by an E3 Ubiquitin Ligase

  摘要：

  本发明涉及双功能化合物，其作为靶向泛素化的调节剂具有实用性，特别是作为本发明的双功能化合物对各种被降解和/或受到抑制的多肽和其他蛋白质的抑制剂。具体而言，本发明涉及含有一端结合泛素连接酶的VHL配体，另一端结合靶蛋白的基团的化合物，使得靶蛋白靠近泛素连接酶以促使该蛋白的降解（和抑制）。本发明展示了与本发明化合物相关的广泛的药理活性范围，与靶向多肽的降解/抑制一致。

  公开号：

  US20140356322A1

文献信息

• COMPOUNDS & METHODS FOR THE ENHANCED DEGRADATION OF TARGETED PROTEINS & OTHER POLYPEPTIDES BY AN E3 UBIQUITIN LIGASE
  申请人：Yale University

  公开号：EP3608317A1

  公开（公告）日：2020-02-12

  The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.

  本发明涉及双功能化合物，它们可作为靶向泛素化的调节剂，特别是可被根据本发明的双功能化合物降解和/或以其他方式抑制的各种多肽和其他蛋白质。特别是，本发明涉及的化合物一端含有与泛素连接酶结合的 VHL 配体，另一端含有与靶蛋白结合的分子，从而使靶蛋白靠近泛素连接酶，以实现对该蛋白的降解（和抑制）。本发明显示了与根据本发明的化合物相关的广泛的药理活性，与降解/抑制靶向多肽一致。
• Compounds and methods for the enhanced degradation of targeted proteins and other polypeptides by an E3 ubiquitin ligase
  申请人：YALE UNIVERSITY

  公开号：US10730862B2

  公开（公告）日：2020-08-04

  The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins that are degraded and/or otherwise inhibited by bifunctional compounds of the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand that binds to the ubiquitin ligase and on the other end a moiety that binds a target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds of the present invention, consistent with the degradation/inhibition of targeted polypeptides.

  本发明涉及双功能化合物，它们可作为靶向泛素化的调节剂，特别是本发明双功能化合物降解和/或以其他方式抑制的各种多肽和其他蛋白质的抑制剂。特别是，本发明涉及的化合物一端含有与泛素连接酶结合的 VHL 配体，另一端含有与靶蛋白结合的分子，从而使靶蛋白靠近泛素连接酶，以达到降解（和抑制）该蛋白的效果。本发明显示了与本发明化合物相关的广泛药理活性，与降解/抑制靶向多肽的作用相一致。
• [EN] COMPOUNDS AND METHODS FOR THE INHIBITION OF VCB E3 UBIQUITIN LIGASE<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR L'INHIBITION DE L'UBIQUITINE LIGASE VCB E3
  申请人：UNIV YALE

  公开号：WO2013106646A3

  公开（公告）日：2013-09-06
• Identification of 5-Substituted 2-Acylaminothiazoles That Activate Tat-Mediated Transcription in HIV-1 Latency Models
  作者：William Nguyen、Jonathan Jacobson、Kate E. Jarman、Helene Jousset Sabroux、Leigh Harty、James McMahon、Sharon R. Lewin、Damian F. Purcell、Brad E. Sleebs

  DOI：10.1021/acs.jmedchem.9b00462

  日期：2019.5.23

  The persistent reservoir of cells latently infected with human immunodeficiency virus (HIV)-integrated proviral DNA necessitates lifelong suppressive antiretroviral therapy (ART). Epigenetic targeted compounds have shown promise as potential latency-reversing agents; however, these drugs have undesirable toxicity and lack specificity for HIV. We utilized a novel HEK293-derived FlpIn dual-reporter cell line, which quantifies specific HIV provirus reactivation (LTR promoter) relative to nonspecific host cell gene expression (CMV promoter), to identify the 5-substituted 2-acylaminothiazole hit class. Here, we describe the optimization of the hit class, defining the functionality necessary for HIV gene activation and for improving in vitro metabolism and solubility. The optimized compounds displayed enhanced HIV gene expression in HEK293 and Jurkat 10.6 latency cellular models and increased unspliced HIV RNA in resting CD4+ T cells isolated from HIV-infected individuals on ART, demonstrating the potential of the 2-acylaminothiazole class as latency-reversing agents.
• COMPOUNDS&METHODS FOR THE ENHANCED DEGRADATION OF TARGETED PROTEINS&OTHER POLYPEPTIDES BY AN E3 UBIQUITIN LIGASE
  申请人：Yale University

  公开号：EP2802608A2

  公开（公告）日：2014-11-19