(R)-3-methyl-2-(1-oxoisoindolin-2-yl)butanoic acid | 298700-69-3

• 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: (R)-3-methyl-2-(1-oxoisoindolin-2-yl)butanoic acid
• 英文别名: (2R)-3-methyl-2-(1-oxo-2,3-dihydro-1H-isoindol-2-yl)butanoic acid；(2R)-3-methyl-2-(3-oxo-1H-isoindol-2-yl)butanoic acid
• CAS: 298700-69-3
• 化学式: C₁₃H₁₅NO₃
• 分子量: 233.267
• InChiKey: JULAETYRRYJIAR-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S,4R)-4-hydroxy-N-(2-hydroxy-4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride 、 (R)-3-methyl-2-(1-oxoisoindolin-2-yl)butanoic 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 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以66%的产率得到(2S,4R)-4-hydroxy-N-(2-hydroxy-4-(4-methylthiazol-5-yl)benzyl)-1-((R)-3-methyl-2-(1-oxoisoindolin-2-yl)butanoyl)pyrrolidine-2-carboxamide
  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：

  D-缬氨酸 、 邻苯二甲醛 以 乙腈 为溶剂， 反应 16.0h， 以0.4 g的产率得到(R)-3-methyl-2-(1-oxoisoindolin-2-yl)butanoic acid
  参考文献：
  名称：

  Erinacerins C–L，异吲哚啉-1-酮具有抑制药用蘑菇猴头菇文化的α-葡萄糖苷酶活性

  摘要：

  众所周知的食用和药用蘑菇猴头菇会产生各种具有生物活性的次生代谢产物。十个新的异吲哚啉-1-酮，称为erinacerins C–L（1 – 10），以及（E）-5-（3,7-二甲基辛基-2,6-dien-1-yl）-4-羟基-6从麻黄的固体培养中分离到-甲氧基-2-苯乙基异吲哚-1-酮（11）。新的代谢物的结构是通过光谱方法建立的。的绝对构型3，4，9和10通过与那些相关的phthalimidines（比较它们的比旋光分配13 -20）。化合物5和6，7和8，和9和10是双键位置异构体。在一个α葡萄糖苷酶抑制测定中，化合物2 - 11显示抑制活性与IC 50个值范围为5.3到145.1微米。初步结构-活性分析表明，萜类化合物侧链和酚羟基大大促进了的α葡萄糖苷酶抑制活性的1 - 11。在细胞毒性分析中，化合物11也呈现弱的细胞毒性对两种细胞系，A549和HeLa，用IC 50 值为49.0和40

  DOI：

  10.1021/np5004388

文献信息

• ESTROGEN-RELATED RECEPTOR ALPHA BASED PROTAC COMPOUNDS AND ASSOCIATED METHODS OF USE
  申请人：Yale University

  公开号：US20160045607A1

  公开（公告）日：2016-02-18

  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 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，其作为靶向泛素化的调节剂具有实用性，特别是根据本发明抑制各种多肽和其他蛋白质的抑制剂。具体而言，本发明涉及一种在一端含有结合泛素连接酶的VHL配体，另一端含有结合靶蛋白的基团的化合物，使得靶蛋白位于靠近泛素连接酶以实现对该蛋白的降解（和抑制）。本发明展示了与根据本发明的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。
• Estrogen-related receptor alpha based protac compounds and associated methods of use
  申请人：Yale University

  公开号：US10071164B2

  公开（公告）日：2018-09-11

  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 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，它们可用作靶向泛素化的调节剂，特别是各种多肽和其他蛋白质的抑制剂，根据本发明的双功能化合物可以降解和/或以其他方式抑制这些多肽和蛋白质。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