(6-isopropoxypyridin-3-yl)methanamine | 195140-88-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (6-isopropoxypyridin-3-yl)methanamine
• 英文别名: [6-(Propan-2-yloxy)pyridin-3-yl]methanamine；(6-propan-2-yloxypyridin-3-yl)methanamine
• CAS: 195140-88-6
• 化学式: C₉H₁₄N₂O
• mdl: MFCD09808644
• 分子量: 166.223
• InChiKey: ZAXOTNRUSOIDKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.444
• 拓扑面积：
  48.1
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  3-(2,6-dimethylphenyl)-5-methyl-1,2-oxazole-4-carboxylic acid 、 (6-isopropoxypyridin-3-yl)methanamine 在 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 生成 1-(3-(2,6-dimethylphenyl)-5-methyl-1,2-oxazol-4-yl)-3-((6-propan-2-yloxypyridin-3-yl)methyl)urea
  参考文献：
  名称：

  苯基异恶唑电压门控钠通道阻滞剂：结构与活性的关系

  摘要：

  某些钠通道的阻塞被认为是治疗慢性疼痛状况的一种有吸引力的机制。苯基异恶唑氨基甲酸酯1被确定为有效的和选择性的Na V 1.7阻滞剂。1的结构类似物（氨基甲酸酯，尿素和酰胺）被证明可用于建立结构与活性的关系并改善ADME相关的性能。酰胺24表现出良好的整体体外特性，可以很好地转化为大鼠体内PK。

  DOI：

  10.1016/j.bmcl.2011.05.041
• 作为产物：
  描述：

  2-异丙基醚-5-氰基吡啶 在 氨 、 氢气 、 镍 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以87.8%的产率得到(6-isopropoxypyridin-3-yl)methanamine
  参考文献：
  名称：

  吡唑并吡啶类化合物或其盐及其制备方法和用途

  摘要：

  本发明涉及吡唑并吡啶类化合物化合物或其盐及其制备方法和用途，尤其涉及其中R1、R2、R3、R4、R5、环A、B、m和n如说明书中所定义的式(I)化合物或者其立体异构体、互变异构体、稳定的同位素衍生物、药学上可接受的盐或溶剂合物，及其制备方法和含有它们的药物组合物，以及所述化合物在制备治疗或预防与RET有关的疾病的药物中的用途。

  公开号：

  CN114181205A

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。
• [EN] ISOINDOLINE DERIVATIVES COMPRISING ADDITIONAL HETEROCYCLIC GROUPS AND THEIR USE IN THE TREATMENT OF PAIN DISORDERS<br/>[FR] DÉRIVÉS ISOINDOLINE COMPRENANT DES GROUPES HÉTÉROCYCLIQUES SUPPLÉMENTAIRES ET LEUR UTILISATION DANS LE TRAITEMENT DE TROUBLES DE LA DOULEUR
  申请人：ASTRAZENECA AB

  公开号：WO2009145720A1

  公开（公告）日：2009-12-03

  Compounds of formula I are claimed wherein R1 is hydrogen; C1-3 alkyl, optionally substituted by one or more substituents independently selected from hydroxy, C1-3 alkoxy andfluoro; C1-3 alkoxy, optionally substituted by one or morefluoro; cyano; hydroxy or halo; m is 1,2 or 3; Het is C5-6 heteroaryl substituted by 1 or 2 substituents R2; R2 is C1-4 alkyl; C1-4 haloalkyl;C 1-4 haloalkoxy; halo; C1-4 alkoxy; or C3-7 cycloalkyloxy, optionally substituted by one or morefluoro; D is C5-6 heteroaryl; C3-7 heterocycloalkyl; or C3-7 cycloalkyl; wherein each D may optionally be substituted by one or more X4; X4 is halo; or C1-3 alkyl, optionally substituted by one or morefluoro; C1-3 alkyl-O-C1-3 alkyl, optionally substituted by one or morefluoro; C1-3 alkoxy, optionally substituted by one or morefluoro; cyano; hydroxy; oxo; R3 0(C=O); or R4(C=O); R3 is C1-4 alkyl; C1-4 alkyl-O-C1-4 alkyl; C5-6 cycloalkyl; aryl; or aryl-C1-2 alkyl; R4 is C1-4 alkyl; or C5-6 heteroaryl; L1is C1-4 alkylene; or a bond; and L2 is C1-3 alkylene. Compounds of the invention are useful in therapy, such as pain therapy.

  式I的化合物被要求，其中R1是氢；C1-3烷基，可选地由一个或多个取代基独立选择自羟基、C1-3烷氧基和氟代基；C1-3烷氧基，可选地由一个或多个氟代基取代；氰基；羟基或卤素基；m为1,2或3；Het是C5-6杂环芳基，取代为1或2个取代基R2；R2是C1-4烷基；C1-4卤代烷基；C1-4卤代烷氧基；卤素；C1-4烷氧基；或C3-7环烷氧基，可选地由一个或多个氟代基取代；D是C5-6杂环芳基；C3-7杂环烷基；或C3-7环烷基；其中每个D可选择地被一个或多个X4取代；X4是卤素；或C1-3烷基，可选地由一个或多个氟代基取代；C1-3烷基-O-C1-3烷基，可选地由一个或多个氟代基取代；C1-3烷氧基，可选地由一个或多个氟代基取代；氰基；羟基；氧代基；R3 0(C=O)；或R4(C=O)；R3是C1-4烷基；C1-4烷基-O-C1-4烷基；C5-6环烷基；芳基；或芳基-C1-2烷基；R4是C1-4烷基；或C5-6杂环芳基；L1是C1-4烷基；或一个键；而L2是C1-3烷基。该发明的化合物在治疗中有用，如疼痛治疗。
• [EN] NEW COMPOUNDS 955<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：ASTRAZENECA AB

  公开号：WO2009010784A1

  公开（公告）日：2009-01-22

  Compounds of formula (I): wherein the substituents are as defined in the specification, are described and claimed. The invention further relates to pharmaceutical compositions containing said compounds and to the use of said compounds in therapy. The present invention also relates to processes for the preparation of said compounds.

  公式(I)的化合物：其中取代基如说明书中所定义，已被描述和声称。本发明进一步涉及包含所述化合物的药物组合物以及所述化合物在治疗中的用途。本发明还涉及制备所述化合物的方法。
• 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。
• 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。