3-hydroxy-4-isopropyl-3-cyclobutene-1,2-dione | 69009-20-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 乙烯基酸
• 英文名称: 3-hydroxy-4-isopropyl-3-cyclobutene-1,2-dione
• 英文别名: 3-Hydroxy-4-isopropyl-3-cyclobuten-1,2-dion；3-Hydroxy-4-propan-2-ylcyclobut-3-ene-1,2-dione
• CAS: 69009-20-7
• 化学式: C₇H₈O₃
• 分子量: 140.139
• InChiKey: RMANDMMQUFAWSX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  甲醇 、 3-hydroxy-4-isopropyl-3-cyclobutene-1,2-dione 以 苯 为溶剂， 以62%的产率得到3-isopropyl-4-methoxycyclobut-3-ene-1,2-dione
  参考文献：
  名称：

  A synthesis of the abietane diterpenoid quinone (±)-royleanone via maleoylcobalt technology.

  摘要：

  DOI：

  10.1016/s0040-4039(00)97454-9
• 作为产物：
  描述：

  3-Isopropoxy-4-isopropyl-3-cyclobutene-1,2-dione 在 amberlyst-15 作用下， 以 乙醇 为溶剂， 反应 12.0h， 以92%的产率得到3-hydroxy-4-isopropyl-3-cyclobutene-1,2-dione
  参考文献：
  名称：

  Inhibitors of Thermus thermophilus Isopropylmalate Dehydrogenase

  摘要：

  In an attempt to use mechanism-based design for the discovery of inhibitors of the isopropylmalate dehydrogenase from T. thermophilus, we have prepared and studied a number of potential mimics for an intermediate in the oxidative decarboxylation of isopropyl malate, the enol or enolate of alpha-ketoisocaproate. Because hydroxamate and dicarboxylate enolate mimics are strong, uncompetitive inhibitors of the enzyme and vinyl fluoride enol mimics are weak, competitive inhibitors, it is suggested that the reaction involves the enolate. The uncompetitive inhibition by a number of anionic compounds suggests, in combination with previous studies in other laboratories, that they mimic the enolate product of the decarboxylation. An explanation for the potency of the inhibition of IMDH by these compounds is proposed based on the electrostatic interaction of product and cofactor.

  DOI：

  10.1021/jo00088a026

文献信息

• [EN] MACROCYCLIC COMPOUNDS FOR INHIBITION OF INHIBITORS OF APOPTOSIS<br/>[FR] COMPOSÉS MACROCYCLIQUES POUR L'INHIBITION D'INHIBITEURS DE L'APOPTOSE
  申请人：ENSEMBLE THERAPEUTICS

  公开号：WO2013071035A1

  公开（公告）日：2013-05-16

  The invention relates generally to macrocyclic compounds and their therapeutic use. More particularly, the invention relates to macrocyclic compounds that modulate the activity of inhibitors of apoptosis (IAPs) and/or are useful in the treatment of medical conditions, such as cancer.

  这项发明通常涉及大环化合物及其治疗用途。更具体地，该发明涉及调节凋亡抑制蛋白（IAPs）活性的大环化合物和/或用于治疗癌症等医疗状况的化合物。
• MACROCYCLIC COMPOUNDS FOR INHIBITION OF INHIBITORS OF APOPTOSIS
  申请人：Ensemble Therapeutics Corp.

  公开号：US20140135270A1

  公开（公告）日：2014-05-15

  There are disclosed compounds that modulate the activity of inhibitors of apoptosis (IAPs), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.

  这里公开了调节凋亡抑制剂（IAPs）活性的化合物，包含所述化合物的药物组合物以及使用本发明的化合物治疗增殖性疾病和凋亡失调疾病的方法，例如癌症。
• Substituted Pyrrolidines and Methods of Use
  申请人：AbbVie S.à.r.l.

  公开号：US20180099931A1

  公开（公告）日：2018-04-12

  The invention discloses compounds of Formula (I) wherein R 1 , R 2 , R 2A , R 3 , R 3A , R 4 , R 4A , and R 5 are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.

  该发明公开了式（I）的化合物 其中R 1 ，R 2 ，R 2A ，R 3 ，R 3A ，R 4 ，R 4A 和R 5 如本文所定义。本发明涉及化合物及其在囊性纤维化治疗中的应用，其生产方法，包含相同化合物的药物组合物，以及通过给予该发明的化合物来治疗囊性纤维化的方法。
• [EN] MACROCYCLIC COMPOUNDS FOR INHIBITION OF INHIBITORS OF APOPTOSIS<br/>[FR] COMPOSÉS MACROCYCLIQUES POUR INHIBITION D'INHIBITEURS DE L'APOPTOSE
  申请人：ENSEMBLE THERAPEUTICS

  公开号：WO2013071027A1

  公开（公告）日：2013-05-16

  The invention relates generally to macrocyclic compounds and their therapeutic use. More particularly, the invention relates to macrocyclic compounds that modulate the activity of inhibitors of apoptosis (IAPs) and/or are useful in the treatment of medical conditions, such as cancer.

  这项发明通常涉及大环化合物及其治疗用途。更具体地，该发明涉及调节凋亡抑制蛋白（IAPs）活性的大环化合物，以及在治疗癌症等医疗状况中有用的大环化合物。
• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF RAPIDLY ACCELERATED FIBROSARCOMA POLYPEPTIDES
  申请人：Arvinas, Inc.

  公开号：US20180179183A1

  公开（公告）日：2018-06-28

  The present disclosure relates to bifunctional compounds, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (RAF, such as c-RAF, A-RAF and/or B-RAF; the 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 RAF, 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, or the constitutive activation 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，其作为快速加速纤维肉瘤（RAF，如c-RAF、A-RAF和/或B-RAF；目标蛋白）的调节剂而发挥作用。具体而言，本公开涉及含有一端为Von Hippel-Lindau、cereblon、凋亡抑制蛋白或鼠双分子同源物2配体的双功能化合物，该配体与相应的E3泛素连接酶结合，并且另一端含有结合目标蛋白RAF的基团，使得目标蛋白与泛素连接酶靠近，以实现目标蛋白的降解（和抑制）。本公开展示了与目标蛋白的降解/抑制相关的广泛药理活性范围。本公开的化合物和组合物用于治疗或预防由目标蛋白的聚集或积累，或目标蛋白的构成性激活导致的疾病或紊乱。