2-(3-oxomorpholino)propanoic acid | 933749-97-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(3-oxomorpholino)propanoic acid
• 英文别名: 2-(3-Oxomorpholino)propanoic acid；2-(3-oxomorpholin-4-yl)propanoic acid
• CAS: 933749-97-4
• 化学式: C₇H₁₁NO₄
• 分子量: 173.169
• InChiKey: TWCJCKIDASUZJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(3-oxomorpholino)propanoic acid 、 (4aS,5aR)-3-(5-bromo-7-fluoro-1H-benzo[d]imidazol-2-yl)-5a-methyl-1,4,4a,5,5a,6-hexahydrocyclopropa[f]indazole 、 碘甲烷 在 sodium hydride 、 2-(三甲基硅烷基)乙氧甲基氯 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 2.5h， 生成 (R)-N-(7-fluoro-2-((4aS,5aR)-5a-methyl-1,4,4a,5,5a,6-hexahydrocyclopropa[f]indazol-3-yl)-1H-benzo[d]imidazol-5-yl)-N-methyl-2-(3-oxomorpholino)propanamide 、 (S)-N-(7-fluoro-2-((4aS,5aR)-5a-methyl-1,4,4a,5,5a,6-hexahydrocyclopropa[f]indazol-3-yl)-1H-benzo[d]imidazol-5-yl)-N-methyl-2-(3-oxomorpholino)propanamide
  参考文献：
  名称：

  [EN] BENZIMIDAZOLE DERIVATIVES
  [FR] DÉRIVÉS DE BENZIMIDAZOLE

  摘要：

  该发明涉及式（I）的苯并咪唑及其药用盐，其中R1至R6如描述中所定义；它们在医学上的应用；含有它们的组合物；它们的制备方法；以及在这些方法中使用的中间体。式（I）的苯并咪唑是ITK抑制剂，因此在治疗包括特应性皮炎在内的广泛疾病中有潜在用途。

  公开号：

  WO2021124155A1
• 作为产物：
  描述：

  benzyl 2-(3-oxomorpholino)propanoate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以93%的产率得到2-(3-oxomorpholino)propanoic acid
  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：US20140356322A1

  公开（公告）日：2014-12-04

  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，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。
• 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
• Chemical Compounds
  申请人：Pfizer Inc.

  公开号：US20210188829A1

  公开（公告）日：2021-06-24

  The invention relates to benzimidazoles of Formula (I) and pharmaceutically acceptable salts thereof, wherein R 1 to R 6 are as defined in the description; to their use in medicine; to compositions containing them; to processes for their preparation; and to intermediates used in such processes. The benzimidazoles of Formula (I) are ITK inhibitors and are therefore potentially useful in the treatment of a wide range of disorders including, atopic dermatitis.