3-(4-amino-2-fluorophenyl)-5-(3,4-dimethoxyphenyl)pyridin-2-amine | 1449301-18-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-(4-amino-2-fluorophenyl)-5-(3,4-dimethoxyphenyl)pyridin-2-amine
• 英文别名: 3-(4-Amino-2-fluorophenyl)-5-(3,4-dimethoxyphenyl)pyridin-2-amine
• CAS: 1449301-18-1
• 化学式: C₁₉H₁₈FN₃O₂
• 分子量: 339.369
• InChiKey: RUDFGVCQAZXNAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  83.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(4-amino-2-fluorophenyl)-5-(3,4-dimethoxyphenyl)pyridin-2-amine 、 5-(4-methylphenyl)-4-oxo-1-(tetrahydro-2H-pyran-4-ylmethyl)-1,4-dihydropyridine-3-carboxylic acid 在 氯化亚砜 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 5.5h， 以46.2%的产率得到N-{4-[2-amino-5-(3,4-dimethoxyphenyl)pyridin-3-yl]-3-fluorophenyl}-5-(4-methylphenyl)-4-oxo-1-(tetrahydro-2H-pyran-4-ylmethyl)-1,4-dihydropyridine-3-carboxamide
  参考文献：
  名称：

  PYRIDONE DERIVATIVE HAVING TETRAHYDROPYRANYLMETHYL GROUP

  摘要：

  本公开提供了新颖的化合物或其盐，或者该化合物或盐的晶体，其抑制Axl并在治疗由Axl高功能引起的疾病、与Axl高功能相关的疾病的治疗和/或涉及Axl高功能的疾病的治疗中有用。本公开提供了具有以下式（I）所代表的四氢吡喃基甲基基团的吡啶酮衍生物，具有各种取代基，或其盐，或化合物或盐的晶体，其中R1、R2、R3、R4、R5、W、X、Y和Z均如规范中定义的。

  公开号：

  US20170183329A1
• 作为产物：
  描述：

  4-氨基-2-氟苯硼酸频那醇酯 在 四(三苯基膦)钯 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 20.0h， 生成 3-(4-amino-2-fluorophenyl)-5-(3,4-dimethoxyphenyl)pyridin-2-amine
  参考文献：
  名称：

  发现一种基于 1,6-naphthyridin-4-one 的 AXL 抑制剂，具有改善的药代动力学和增强的体内抗肿瘤功效

  摘要：

  受体酪氨酸激酶AXL 已成为抗癌药物发现中有吸引力的靶标。在此，我们描述了一系列新的 1,6-naphthyridin-4-one 衍生物作为有效 AXL 抑制剂的发现。从我们小组先前报道的低体内效力化合物9开始，我们利用基于结构的药物设计和支架跳跃策略来发现有效的 AXL 抑制剂。专有化合物13c是一种高效且可口服生物利用的 AXL 抑制剂，IC 50值为 3.2 ± 0.3 nM。化合物13c在 AXL 驱动的肿瘤异种移植小鼠中表现出显着改善的体内抗肿瘤功效，在耐受良好的剂量下引起肿瘤消退，并在 Sprague 中表现出良好的药代动力学特性（MRT = 16.5 h，AUC 0-∞ = 59,815 ng h/mL） -道利鼠。这些结果表明13c是 AXL 靶向癌症治疗的有前途的候选药物。

  DOI：

  10.1016/j.ejmech.2023.116045

文献信息

• Pyridone Derivatives
  申请人：DAIICHI SANKYO COMPANY, LIMITED

  公开号：US20130281428A1

  公开（公告）日：2013-10-24

  Novel compounds or salts thereof, or crystals thereof, which inhibit Axl and are useful for treating diseases caused by Axl hyperfunction, diseases associated with Axl hyperfunction and/or diseases accompanied by Axl hyperfunction are provided. Pyridone derivatives represented by the formula (1) having various substituents or salts thereof, or crystals thereof (where R 1 , R 2 , R 3 , R 5 , R 6 , A, W, X and n in the formula (1) are as defined in the specification, respectively) are provided.

  提供了抑制Axl并用于治疗由Axl高功能引起的疾病、与Axl高功能相关的疾病和/或伴随Axl高功能的疾病的新型化合物或其盐，或其晶体。提供了由式（1）所代表的吡啶酮衍生物，具有各种取代基或其盐，或其晶体（其中式（1）中的R1、R2、R3、R5、R6、A、W、X和n分别如规范中定义）。
• COMPOUND HAVING AXL AND C-MET KINASE INHIBITORY ACTIVITY, PREPARATION THEREOF AND APPLICATION THEREOF
  申请人：Shanghai Institute of Materia Medica, Chinese Academy of Sciences

  公开号：EP4029862A1

  公开（公告）日：2022-07-20

  A compound having Axl and c-Met kinase inhibitory activity, a preparation method therefor and an application thereof. Specifically, a compound having the structure represented by formula (I), a preparation method therefor and an application thereof in the preparation of a medication for the treatment and/or prevention of tumor-associated diseases and/or kinase-related diseases.

  具有Axl和c-Met激酶抑制活性的化合物，其制备方法及其应用。具体来说，该化合物具有由式（I）表示的结构，其制备方法及其在制备用于治疗和/或预防与肿瘤相关的疾病和/或激酶相关疾病的药物中的应用。
• PYRIDONE DERIVATIVE HAVING TETRAHYDROPYRANYL METHYL GROUP
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP3168219A1

  公开（公告）日：2017-05-17

  It is intended to provide a novel compound or a salt thereof, or crystals of the compound or the salt, which inhibit Axl and are useful in the treatment of a disease caused by hyperfunction of Axl, the treatment of a disease associated with hyperfunction of Axl, and/or the treatment of a disease involving hyperfunction of Axl. [Solution] The present invention provides a pyridone derivative having a tetrahydropyranylmethyl group represented by the following formula (I) having various substituents, or a salt thereof, or crystals of the compound or the salt (wherein R1, R2, R3, R4, R5, W, X, Y, and Z are each as defined in the specification).

  本发明旨在提供一种新型化合物或其盐，或该化合物或其盐的结晶，该化合物或其盐可抑制 Axl，并可用于治疗由 Axl 功能亢进引起的疾病、治疗与 Axl 功能亢进相关的疾病和/或治疗涉及 Axl 功能亢进的疾病。 [解决方案］ 本发明提供一种吡啶酮衍生物，该衍生物具有下式（I）所代表的具有各种取代基的四氢吡喃甲基，或其盐，或该化合物或该盐的结晶（其中R1、R2、R3、R4、R5、W、X、Y和Z各自如说明书中所定义）。
• MULTI-SUBSTITUTED PYRIDONE DERIVATIVES AND MEDICAL USE THEREOF
  申请人：Beijing Yuezhikangtai Biomedicines Co., Ltd.

  公开号：EP3845527A1

  公开（公告）日：2021-07-07

  The present invention relates to multi-substituted pyridone derivatives and therapeutic use thereof. In particular, the present invention relates to a compound of formula (I), a preparation method therefor, a pharmaceutical composition comprising the same, as well as use thereof as a tyrosine kinase inhibitor, in particular, use thereof in treating a disease associated with tyrosine kinase activity. Each substituent in the formula (I) is defined as in the specification.

  本发明涉及多取代吡啶酮衍生物及其治疗用途。特别是，本发明涉及式（I）化合物、其制备方法、包含其的药物组合物以及其作为酪氨酸激酶抑制剂的用途，尤其是其在治疗与酪氨酸激酶活性相关的疾病中的用途。式（I）中各取代基的定义见说明书。
• Pyridone derivatives having tetrahydropyranylmethyl groups
  申请人：DAIICHI SANKYO COMPANY, LIMITED

  公开号：US10442797B2

  公开（公告）日：2019-10-15

  The present disclosure provides novel compounds or salts thereof, or crystals of the compounds or the salts, which inhibit Axl and are useful in the treatment of a disease caused by hyperfunction of Axl, the treatment of a disease associated with hyperfunction of Axl, and/or the treatment of a disease involving hyperfunction of Axl. The present disclosure provides pyridone derivatives having a tetrahydropyranylmethyl group represented by the following formula (I) having various substituents, or salts thereof, or crystals of the compounds or the salts, wherein R1, R2, R3, R4, R5, W, X, Y, and Z are each as defined in the specification:

  本公开提供了新型化合物或其盐，或化合物或其盐的结晶，它们抑制Axl，可用于治疗由Axl功能亢进引起的疾病、治疗与Axl功能亢进相关的疾病和/或治疗涉及Axl功能亢进的疾病。 本公开提供了具有下式(I)所代表的具有各种取代基的四氢吡喃甲基的吡啶酮衍生物，或其盐，或化合物或其盐的结晶，其中R1、R2、R3、R4、R5、W、X、Y和Z各自如说明书中所定义：