(2S,4S)-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-4-[[4-[4-[4-[[(3S,5S)-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-5-[(4-phenylthiadiazol-5-yl)carbamoyl]pyrrolidin-3-yl]oxymethyl]phenyl]buta-1,3-diynyl]phenyl]methoxy]-N-(4-phenylthiadiazol-5-yl)pyrrolidine-2-carboxamide | 1073560-27-6

• 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: (2S,4S)-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-4-[[4-[4-[4-[[(3S,5S)-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-5-[(4-phenylthiadiazol-5-yl)carbamoyl]pyrrolidin-3-yl]oxymethyl]phenyl]buta-1,3-diynyl]phenyl]methoxy]-N-(4-phenylthiadiazol-5-yl)pyrrolidine-2-carboxamide
• CAS: 1073560-27-6
• 化学式: C₆₈H₇₈N₁₂O₈S₂
• 分子量: 1255.57
• InChiKey: UDNWZMRBTMHLQU-JGEIRJKBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.4
• 重原子数：
  90
• 可旋转键数：
  25
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  308
• 氢给体数：
  6
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (2S,4S)-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-4-[[4-[4-[4-[[(3S,5S)-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-5-[(4-phenylthiadiazol-5-yl)carbamoyl]pyrrolidin-3-yl]oxymethyl]phenyl]buta-1,3-diynyl]phenyl]methoxy]-N-(4-phenylthiadiazol-5-yl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  WO2008/134679

  摘要：

  公开号：

文献信息

• TETRAHYDRONAPHTHALENE AND TETRAHYDROISOQUINOLINE DERIVATIVES AS ESTROGEN RECEPTOR DEGRADERS
  申请人：Arvinas, Inc.

  公开号：US20180155322A1

  公开（公告）日：2018-06-07

  The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, Inhibitors of Apoptosis Proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，这些化合物可用作雌激素受体（目标蛋白）的调节剂。特别是，本公开涉及包含在一段至少有一种Von Hippel-Lindau配体、一种cereblon配体、凋亡抑制蛋白配体、小鼠双分钟同源2配体或其组合的双功能化合物，这些配体与相应的E3泛素连接酶结合，在另一端有一个与目标蛋白结合的部分，使得目标蛋白被置于泛素连接酶附近，以实现目标蛋白的降解（和抑制）。本公开展示了与目标蛋白降解/抑制相关的广泛药理活性。可以通过本公开的化合物和组合物治疗或预防由目标蛋白聚集或积累引起的疾病或障碍。
• Tetrahydronaphthalene and tetrahydroisoquinoline derivatives as estrogen receptor degraders
  申请人：Arvinas, Inc.

  公开号：US10647698B2

  公开（公告）日：2020-05-12

  The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, Inhibitors of Apoptosis Proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，它们可用作雌激素受体（靶蛋白）的调节剂。特别是，本公开涉及双功能化合物，其一端含有 Von Hippel-Lindau 配体、cereblon 配体、凋亡蛋白抑制剂配体、小鼠双敏同源物 2 配体或其组合中的至少一种、其一端与相应的 E3 泛素连接酶结合，另一端与靶蛋白结合，从而将靶蛋白置于泛素连接酶附近，以实现对靶蛋白的降解（和抑制）。本公开物具有与降解/抑制靶蛋白相关的广泛药理活性。本公开的化合物和组合物可以治疗或预防因目标蛋白聚集或积聚而导致的疾病或失调。
• Compounds and methods for the targeted degradation of fetal liver kinase polypeptides
  申请人：Arvinas Operations, Inc.

  公开号：US10806737B2

  公开（公告）日：2020-10-20

  The present disclosure relates to bifunctional compounds, which find utility as modulators of FLT3 (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hppel-Lindau, cereblon, ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds the target protein FLT3, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of the target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，它们可用作 FLT3（靶蛋白）的调节剂。特别是，本公开涉及双功能化合物，其一端含有与 E3 泛素连接酶结合的 Von Hppel-Lindau（脑龙）配体，另一端含有与靶蛋白 FLT3 结合的分子，从而将靶蛋白置于泛素连接酶附近，以实现对靶蛋白的降解（和抑制）。本公开物具有与降解/抑制靶蛋白相关的广泛药理活性。本公开的化合物和组合物可以治疗或预防因目标蛋白聚集或积聚而导致的疾病或失调。
• Modulators of BTK proteolysis and methods of use
  申请人：Yale University

  公开号：US11028088B2

  公开（公告）日：2021-06-08

  The present disclosure relates to bifunctional compounds, which find utility as modulators of Burton's Tyrosine Kinase (BTK). In particular, the present disclosure is directed to bifunctional compounds. One end of a bifunctional compound includes a Von Hippel-Lindau, Cereblon, Inhibitors of Apotosis Proteins, or Mouse Double-Minute Homolog 2 ligand that binds to the respective E3 ubiquitin ligase. The other end of a bifunctional compound includes 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 target protein. Diseases or disorders that result from aggregation, accumulation, and/or overactivation of the target protein can be treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，这些化合物可用作伯顿酪氨酸激酶（BTK）的调节剂。特别是，本公开涉及双功能化合物。双功能化合物的一端包括与相应 E3 泛素连接酶结合的 Von Hippel-Lindau、Cereblon、抑制细胞凋亡蛋白或小鼠双敏同源物 2 配体。双功能化合物的另一端包括与靶蛋白结合的分子，这样靶蛋白就会被置于泛素连接酶附近，以实现对靶蛋白的降解（和抑制）。本公开的化合物和组合物可以治疗或预防由于靶蛋白的聚集、积累和/或过度激活而导致的疾病或失调。
• Modulators of proteolysis and associated methods of use
  申请人：Arvinas Operations, Inc.

  公开号：US11161841B2

  公开（公告）日：2021-11-02

  The present disclosure relates to bifunctional compounds, which find utility as modulators of Kirsten rat sarcoma protein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation, accumulation, and/or overactivation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，它们可用作 Kirsten 大鼠肉瘤蛋白（靶蛋白）的调节剂。特别是，本公开涉及双功能化合物，其一端含有与相应 E3 泛素连接酶结合的 Von Hippel-Lindau、cereblon、Apotosis Proteins 抑制剂或小鼠双敏同源物 2 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靶蛋白的降解（和抑制）。本公开物具有与降解/抑制靶蛋白相关的广泛药理活性。本公开的化合物和组合物可以治疗或预防因目标蛋白的聚集、积累和/或过度激活而导致的疾病或失调。