(7S,8R,9S,13S,14S,17S)-7-(4-(2-(2-(benzyloxy)ethoxy)ethoxy)butyl)-3,17-bis(methoxymethoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-6-one | 1448189-05-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (7S,8R,9S,13S,14S,17S)-7-(4-(2-(2-(benzyloxy)ethoxy)ethoxy)butyl)-3,17-bis(methoxymethoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-6-one
• 英文别名: (7S,8R,9S,13S,14S,17S)-7-(4-(2-(2-(Benzyloxy)ethoxy)ethoxy)butyl)-3,17-bis(methoxymethoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-6-one；(7S,8R,9S,13S,14S,17S)-3,17-bis(methoxymethoxy)-13-methyl-7-[4-[2-(2-phenylmethoxyethoxy)ethoxy]butyl]-8,9,11,12,14,15,16,17-octahydro-7H-cyclopenta[a]phenanthren-6-one
• CAS: 1448189-05-6
• 化学式: C₃₇H₅₂O₈
• 分子量: 624.815
• InChiKey: GYEIFJLKXRDGPB-MGGLRHJGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  45
• 可旋转键数：
  19
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  81.7
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (7S,8R,9S,13S,14S,17S)-7-(4-(2-(2-(benzyloxy)ethoxy)ethoxy)butyl)-3,17-bis(methoxymethoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-6-one 在 盐酸 、 三乙基硅烷 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 102.0h， 生成 (7R,8R,9S,13S,14S,17S)-7-(4-(2-(2-(benzyloxy)ethoxy)ethoxy)butyl)-3,17-bis(methoxymethoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene
  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：

  二乙二醇单苯甲醚 在 potassium tert-butylate 、 sodium hydride 、 sodium iodide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 丙酮 、 mineral oil 为溶剂， 反应 5.7h， 生成 (7S,8R,9S,13S,14S,17S)-7-(4-(2-(2-(benzyloxy)ethoxy)ethoxy)butyl)-3,17-bis(methoxymethoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-6-one
  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
• [EN] COMPOUNDS & METHODS FOR THE ENHANCED DEGRADATION OF TARGETED PROTEINS & OTHER POLYPEPTIDES BY AN E3 UBIQUITIN LIGASE<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR LA DÉGRADATION AMÉLIORÉE DE PROTÉINES CIBLES ET D'AUTRES POLYPEPTIDES PAR UNE E3 UBIQUITINE LIGASE
  申请人：UNIV YALE

  公开号：WO2013106643A2

  公开（公告）日：2013-07-18

  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.