tert-butyl 4-(4-cyano-3-(methoxycarbonyl)phenyl)piperazine-1-carboxylate | 1345628-09-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(4-cyano-3-(methoxycarbonyl)phenyl)piperazine-1-carboxylate
• 英文别名: tert-Butyl 4-(4-cyano-3-(methoxycarbonyl)phenyl)piperazine-1-carboxylate；tert-butyl 4-(4-cyano-3-methoxycarbonylphenyl)piperazine-1-carboxylate
• CAS: 1345628-09-2
• 化学式: C₁₈H₂₃N₃O₄
• 分子量: 345.398
• InChiKey: SAHGSNVBPWJTIF-UHFFFAOYSA-N

物化性质

• 沸点：
  510.4±50.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  82.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4-cyano-3-(methoxycarbonyl)phenyl)piperazine-1-carboxylate 在 palladium 10% on activated carbon 、 氢气 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.5h， 生成 tert-butyl 4-(2-ethyl-3-oxo-2,3-dihydro-1H-isoindol-5-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationships of spirolactones bearing 2-ureidobenzothiophene as acetyl-CoA carboxylases inhibitors

  摘要：

  The co-crystal structure of the human acetyl-coenzyme A 2 (ACC2) carboxyl transferase domain and the reported compound CP-640186 (1b) suggested that two carbonyl groups are essential for potent ACC2 inhibition. By focusing on enhancing the interactions between the two carbonyl groups and the amino acid residues Gly(2162) and Glu(2230), we used ligand-and structure-based drug design to discover spirolactones bearing a 2-ureidobenzothiophene moiety (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.117
• 作为产物：
  描述：

  2-氰基-5-氟苯甲酸甲酯 、 N-Boc-哌嗪 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 24.0h， 以46%的产率得到tert-butyl 4-(4-cyano-3-(methoxycarbonyl)phenyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationships of spirolactones bearing 2-ureidobenzothiophene as acetyl-CoA carboxylases inhibitors

  摘要：

  The co-crystal structure of the human acetyl-coenzyme A 2 (ACC2) carboxyl transferase domain and the reported compound CP-640186 (1b) suggested that two carbonyl groups are essential for potent ACC2 inhibition. By focusing on enhancing the interactions between the two carbonyl groups and the amino acid residues Gly(2162) and Glu(2230), we used ligand-and structure-based drug design to discover spirolactones bearing a 2-ureidobenzothiophene moiety (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.117

文献信息

• 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。
• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR AND ASSOCIATED METHODS OF USE
  申请人：Arvinas Operations, Inc.

  公开号：US20220144809A1

  公开（公告）日：2022-05-12

  Bifunctional compounds, which find utility as modulators of androgen receptor (AR), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds AR, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本文描述了具有雄激素受体（AR）调节剂作用的双功能化合物。特别地，本公开的双功能化合物在一端含有结合到cereblon E3泛素连接酶的基团，在另一端含有结合到AR的基团，使得靶蛋白质位于泛素连接酶附近以促进靶蛋白质的降解（和抑制）。本公开的双功能化合物表现出与靶蛋白质的降解/抑制相关的广泛的药理活性。使用本公开的化合物和组合物治疗或预防由靶蛋白质异常调节引起的疾病或障碍。
• [EN] COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR AND ASSOCIATED METHODS OF USE<br/>[FR] COMPOSÉS ET MÉTHODES POUR LA DÉGRADATION CIBLÉE DU RÉCEPTEUR DES ANDROGÈNES ET MÉTHODES D'UTILISATION ASSOCIÉES
  申请人：ARVINAS OPERATIONS INC

  公开号：WO2022098544A1

  公开（公告）日：2022-05-12

  Bifunctional compounds, which find utility as modulators of androgen receptor (AR), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds AR, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure..

  本文描述了具有雄激素受体（AR）调节剂作用的双功能化合物。具体而言，本公开的双功能化合物在一端包含结合到 cereblon E3 泛素连接酶的一个部分，在另一端包含结合 AR 的一个部分，从而使目标蛋白质靠近泛素连接酶，以促进目标蛋白质的降解（和抑制）。本公开的双功能化合物表现出与目标蛋白质的降解/抑制相关的广泛药理活性。使用本公开的化合物和组合物治疗或预防由于目标蛋白质异常调节而导致的疾病或障碍。
• Compounds and methods for the targeted degradation of androgen receptor
  申请人：Arvinas Operations, Inc.

  公开号：US10844021B2

  公开（公告）日：2020-11-24

  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，它们可用于降解和（抑制）雄激素受体。特别是，本公开涉及的化合物一端含有与 E3 泛素连接酶结合的脑龙配体，另一端含有与雄激素受体结合的分子，这样雄激素受体就被置于泛素连接酶附近，从而实现对雄激素受体的降解（和抑制）。本公开的化合物具有广泛的药理活性，与雄激素受体的降解/抑制作用相一致。
• [EN] COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR LA DÉGRADATION CIBLÉE DU RÉCEPTEUR DES ANDROGÈNES
  申请人：ARVINAS INC

  公开号：WO2018071606A1

  公开（公告）日：2018-04-19

  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.