3-(tert-butyl)quinazolin-4(3H)-one | 113260-96-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3-(tert-butyl)quinazolin-4(3H)-one
• 英文别名: 3-tert-butylquinazolin-4(3H)-one；3-tert-butylquinazolin-4-one
• CAS: 113260-96-1
• 化学式: C₁₂H₁₄N₂O
• 分子量: 202.256
• InChiKey: RHIUXFJPXJOQMK-UHFFFAOYSA-N

物化性质

• 熔点：
  65-66 °C(Solv: ethanol (64-17-5))
• 沸点：
  320.5±25.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  苯乙酮对甲苯磺酰腙 、 3-(tert-butyl)quinazolin-4(3H)-one 在 2,2'-联吡啶 、 copper(l) iodide 、 lithium tert-butoxide 作用下， 以 甲苯 为溶剂， 反应 6.0h， 以86%的产率得到3-(tert-butyl)-2-(1-phenylethyl)quinazolin-4(3H)-one
  参考文献：
  名称：

  铜（I）/ Bpy催化​​喹唑啉-4（3H）-one与N-甲苯磺酰hydr的C-2-H苯甲酰化

  摘要：

  研究了在依赖配体的铜体系中，喹唑啉-4（3 H）-酮与N-甲苯磺酰hydr的区域选择性C-2-H苄基化。将一系列取代的喹唑啉-4（3 H）-酮与衍生自芳基酮的各种N-甲苯磺酰hydr有效地偶联，以中等至良好的产率提供烷基化产物。这是构造C（sp 2）–C（sp 3）键的有用，省时且可扩展的过程。

  DOI：

  10.1002/ejoc.202000244
• 作为产物：
  描述：

  邻氨基苯甲酸 在 对甲苯磺酸 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 3-(tert-butyl)quinazolin-4(3H)-one
  参考文献：
  名称：

  Gupton, John T.; Miller, John F.; Bryant, Robert D., Tetrahedron, 1987, vol. 43, # 8, p. 1747 - 1752

  摘要：

  DOI：

文献信息

• BRM TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE
  申请人：Arvinas Operations, Inc.

  公开号：US20190300521A1

  公开（公告）日：2019-10-03

  The present disclosure relates to bifunctional compounds, which find utility as modulators of SMARCA2 or BRM (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand that binds to the Von Hippel-Lindau 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，其作为SMARCA2或BRM（靶蛋白）的调节剂具有实用性。具体而言，本公开涉及包含一端结合Von Hippel-Lindau E3泛素连接酶的配体，另一端结合靶蛋白的双功能化合物，使得靶蛋白与泛素连接酶靠近以实现靶蛋白的降解（和抑制）。本公开展示了与靶蛋白降解/抑制相关的广泛药理活性。本公开的化合物和组合物用于治疗或预防由靶蛋白聚集或积累导致的疾病或紊乱。
• TAU-PROTEIN TARGETING PROTACS AND ASSOCIATED METHODS OF USE
  申请人：Arvinas, Inc.

  公开号：US20180125821A1

  公开（公告）日：2018-05-10

  The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau 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tau蛋白的调节剂具有实用性。具体而言，本公开涉及含有一端结合到E3泛素连接酶的VHL或cereblon配体，另一端结合到tau蛋白的双功能化合物，使得tau蛋白与泛素连接酶靠近，以实现tau蛋白的降解（和抑制）。本公开展示了与tau蛋白降解/抑制相关的广泛药理活性。本公开的化合物和组合物用于治疗或预防由tau蛋白聚集或积累导致的疾病或紊乱。
• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE 4 POLYPEPTIDES
  申请人：Arvinas, Inc.

  公开号：US20190151295A1

  公开（公告）日：2019-05-23

  The present disclosure relates to bifunctional compounds, which find utility as modulators of Interleukin-1 Receptor-Associated Kinase 4 (IRAK-4); the 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, 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，其作为白细胞介素-1受体相关激酶4（IRAK-4；目标蛋白）的调节剂具有实用性。具体而言，本公开涉及包含一端结合E3泛素连接酶的Von Hppel-Lindau、cereblon配体的双功能化合物，另一端结合目标蛋白的部分，使得目标蛋白靠近泛素连接酶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。本公开的化合物和组合物用于治疗或预防由目标蛋白聚集或积累导致的疾病或紊乱。
• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR
  申请人：Arvinas, Inc.

  公开号：US20180099940A1

  公开（公告）日：2018-04-12

  The present disclosure relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor.

  本公开涉及双功能化合物，其用于降解和（抑制）雄激素受体。具体而言，本公开涉及包含一端结合到E3泛素连接酶的谷氨酰腺苷环配体，另一端结合到雄激素受体的部分的化合物，使得雄激素受体与泛素连接酶靠近，以实现雄激素受体的降解（和抑制）。本公开展示了与根据本公开涉及的化合物相关的广泛的药理活性范围，与雄激素受体的降解/抑制一致。
• CEREBLON LIGANDS AND BIFUNCTIONAL COMPOUNDS COMPRISING THE SAME
  申请人：Arvinas, Inc.

  公开号：US20180215731A1

  公开（公告）日：2018-08-02

  The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, 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 disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 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. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

  该描述涉及cereblon E3连接酶结合化合物，包括包含相同成分的双功能化合物，这些化合物作为靶向泛素化的调节剂具有实用价值，尤其是抑制剂，可降解和/或以其他方式抑制根据本公开的双功能化合物。特别是，该描述提供了化合物，其一端含有与cereblon E3泛素连接酶结合的配体，另一端含有与目标蛋白结合的部分，使目标蛋白位于泛素连接酶附近以降解（和抑制）该蛋白。可以合成表现出广泛药理活性的化合物，与几乎所有类型的靶向多肽的降解/抑制一致。