1-(4-氟-3-硝基苄基)哌啶 | 509093-74-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 1-(4-氟-3-硝基苄基)哌啶
• 英文名称: 1-[(4-fluoro-3-nitrophenyl)methyl]piperidine
• 英文别名: 1-(4-fluoro-3-nitro-benzyl)-piperidine；1-(4-Fluoro-3-nitrobenzyl)piperidine
• CAS: 509093-74-7
• 化学式: C₁₂H₁₅FN₂O₂
• 分子量: 238.262
• InChiKey: ODCAALVDGZDACW-UHFFFAOYSA-N

物化性质

• 沸点：
  346.6±27.0 °C(Predicted)
• 密度：
  1.241±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-氟-3-硝基苄基)哌啶 在 氯化铵 、 N,N-二异丙基乙胺 、 锌 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 20.0h， 生成 ethyl (1s,4s)-4-(2-amino-5-(piperidin-1-ylmethyl)-1H-benzo[d]imidazol-1-yl)cyclohexane-1-carboxylate
  参考文献：
  名称：

  COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE 4 POLYPEPTIDES

  摘要：

  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。

  公开号：

  US20190151295A1
• 作为产物：
  描述：

  4-氟-3-硝基苄醇 在 sodium hypochlorite 、 2,2,6,6-四甲基哌啶氧化物 、 三乙酰氧基硼氢化钠 、 溶剂黄146 、 potassium bromide 作用下， 以 二氯甲烷 、 水 、 1,2-二氯乙烷 为溶剂， 生成 1-(4-氟-3-硝基苄基)哌啶
  参考文献：
  名称：

  Discovery of potent, selective, and orally bioavailable inhibitors of interleukin-1 receptor-associate kinase-4

  摘要：

  In this Letter, we report the continued optimization of the N-acyl-2-aminobenzimidazole series, focusing in particular on the N-alkyl substituent and 5-position of the benzimidazole based on the binding mode and the early SAR. These efforts led to the discovery of 16, a highly potent, selective, and orally bioavailable inhibitor of IRAK-4. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.10.060

文献信息

• 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。
• Indazole derivatives as modulators of interleukin-1 receptor-associated kinase
  申请人：Guckian Kevin

  公开号：US20110152260A1

  公开（公告）日：2011-06-23

  The present invention relates to modulators of IRAK kinases of formula (I) and provides compositions comprising such modulators, as well as methods therewith for treating IRAK-mediated or IRAK-associated conditions or diseases.

  本发明涉及公式（I）的IRAK激酶调节剂，并提供包含这种调节剂的组合物，以及用于治疗IRAK介导或与IRAK相关的疾病或病症的方法。
• Benzimidazole derivatives
  申请人：Tularik, Inc

  公开号：US20030144286A1

  公开（公告）日：2003-07-31

  Compounds, pharmaceutical compositions and methods are provided that are useful in the treatment of inflammatory and immune-related conditions or disorders. In particular, the invention provides compounds which modulate the expression and/or function of proteins involved in inflammation, immune response regulation and cell proliferation. The subject compounds are 2-amino-imidazole derivatives.

  提供了在治疗炎症和免疫相关疾病或疾病中有用的化合物、药物组合物和方法。具体来说，该发明提供了调节参与炎症、免疫反应调节和细胞增殖的蛋白质的表达和/或功能的化合物。这些化合物是2-氨基咪唑衍生物。
• BENZIMIDAZOLE DERIVATIVES
  申请人：Frenkel Alexander David

  公开号：US20100048565A1

  公开（公告）日：2010-02-25

  Compounds, pharmaceutical compositions and methods are provided that are useful in the treatment of inflammatory and immune-related conditions or disorders. In particular, the invention provides compounds which modulate the expression and/or function of proteins involved in inflammation, immune response regulation and cell proliferation. The subject compounds are 2-amino-imidazole derivatives.

  本发明提供了在治疗炎症和免疫相关的疾病或疾病中有用的化合物、制药组合物和方法。特别地，本发明提供了能够调节参与炎症、免疫反应调节和细胞增殖的蛋白质的表达和/或功能的化合物。这些化合物是2-氨基咪唑衍生物。
• Compounds and methods for the targeted degradation of interleukin-1 receptor- associated kinase 4 polypeptides
  申请人：Arvinas Operations, Inc.

  公开号：US11065231B2

  公开（公告）日：2021-07-20

  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，这些化合物可作为白细胞介素-1受体相关激酶4（IRAK-4）（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聚集或积聚而导致的疾病或失调。