6-(6-chloroimidazo[1,2-a]pyridin-3-yl)-N-(pyrrolidin-3-yl)pyridin-2-amine | 1044733-38-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 6-(6-chloroimidazo[1,2-a]pyridin-3-yl)-N-(pyrrolidin-3-yl)pyridin-2-amine
• 英文别名: IRAK4 inhibitor rac-45；6-(6-chloroimidazo[1,2-a]pyridin-3-yl)-N-pyrrolidin-3-ylpyridin-2-amine
• CAS: 1044733-38-1
• 化学式: C₁₆H₁₆ClN₅
• 分子量: 313.79
• InChiKey: NAMQQRIYZTTYCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  54.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 盐酸 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 生成 6-(6-chloroimidazo[1,2-a]pyridin-3-yl)-N-(pyrrolidin-3-yl)pyridin-2-amine
  参考文献：
  名称：

  IRAK-4抑制剂。第三部分：一系列咪唑并[1,2-a]吡啶。

  摘要：

  通过常规的项目交叉筛选鉴定出有效的IRAK抑制剂后，建立了新型的IRAK-4抑制剂。探索了咪唑并[1,2-a]吡啶基吡啶和苯并咪唑并吡啶的SAR。

  DOI：

  10.1016/j.bmcl.2008.04.042

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。
• Therapeutic Combinations of an IRAK4 Inhibitor and a BTK Inhibitor
  申请人：Acerta Pharma B.V.

  公开号：US20170035881A1

  公开（公告）日：2017-02-09

  Therapeutic combinations of an interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of an IRAK4 inhibitor and a BTK inhibitor, and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer.

  描述了一种白细胞介素-1受体相关激酶4（IRAK4）抑制剂和布鲁顿酪氨酸激酶（BTK）抑制剂的治疗组合。在某些实施例中，本发明提供了包含IRAK4抑制剂和BTK抑制剂组合的药物组合物，以及使用这些药物组合物治疗疾病，特别是癌症的方法。
• IMIDAZO[1,2-A]PYRIDINE COMPOUNDS, COMPOSITIONS COMPRISING THEM, METHODS FOR TREATING DISEASES USING THEM, AND METHODS FOR PREPARING THEM
  申请人：Children's Hospital Medical Center

  公开号：EP3854796A1

  公开（公告）日：2021-07-28

  Some embodiments of the invention include inventive compounds (e.g., compounds of Formula (I)). Other embodiments include compositions (e.g., pharmaceutical compositions) comprising the inventive compound. Still other embodiments of the invention include compositions (e.g., pharmaceutical compositions) for treating, for example, certain diseases using the inventive compounds. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as cancer or blood disorders). Further embodiments include methods for making the inventive compounds. Additional embodiments of the invention are also discussed herein.

  本发明的一些实施方案包括本发明化合物（如式（I）化合物）。其它实施方案包括包含本发明化合物的组合物（如药物组合物）。本发明的另一些实施方案包括使用本发明化合物治疗例如某些疾病的组合物（例如药物组合物）。一些实施方案包括使用本发明化合物（例如在组合物中或在药物组合物中）施用和治疗（例如癌症或血液疾病等疾病）的方法。进一步的实施方案包括制造本发明化合物的方法。本文还讨论了本发明的其它实施方案。
• 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。
• Substituted imidazo[1,2-A]pyridines as IRAK 1/4 and flt3 inhibitors
  申请人：CHILDREN'S HOSPITAL MEDICAL CENTER

  公开号：US11254667B2

  公开（公告）日：2022-02-22

  Some embodiments of the invention include inventive compounds (e.g., compounds of Formula (I)). Other embodiments include compositions (e.g., pharmaceutical compositions) comprising the inventive compound. Still other embodiments of the invention include compositions (e.g., pharmaceutical compositions) for treating, for example, certain diseases using the inventive compounds. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as cancer or blood disorders). Further embodiments include methods for making the inventive compounds. Additional embodiments of the invention are also discussed herein.

  本发明的一些实施方案包括本发明化合物（如式（I）化合物）。其它实施方案包括包含本发明化合物的组合物（如药物组合物）。本发明的另一些实施方案包括使用本发明化合物治疗例如某些疾病的组合物（例如药物组合物）。一些实施方案包括使用本发明化合物（例如在组合物中或在药物组合物中）施用和治疗（例如癌症或血液疾病等疾病）的方法。进一步的实施方案包括制造本发明化合物的方法。本文还讨论了本发明的其它实施方案。