N-(2-氯-5-甲氧基苯基)-6-甲氧基 | 476159-98-5

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: N-(2-氯-5-甲氧基苯基)-6-甲氧基
• 英文名称: N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine
• 英文别名: AZM475271；M 475271；N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine
• CAS: 476159-98-5
• 化学式: C₂₃H₂₇ClN₄O₃
• 分子量: 442.945
• InChiKey: WPOXAFXHRJYEIC-UHFFFAOYSA-N

物化性质

• 沸点：
  556.1±50.0 °C(Predicted)
• 密度：
  1.252±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO：43.15（最大浓度 mg/mL）；97.42（最大浓度 mM）

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  68.7
• 氢给体数：
  1
• 氢受体数：
  7

制备方法与用途

生物活性方面，AZM475271 是一种高效的 Src 激酶选择性抑制剂，其 IC50 值仅为 5 nM。然而，它对 Flt3、KDR 和 Tie-2 的抑制作用较弱（IC50 > 10 μM）。

反应信息

• 作为产物：
  描述：

  2-氯-5-甲氧基苯胺 、 4-氯-6-甲氧基-7-[(1-甲基-4-哌啶基)甲氧基]-喹唑烷 在 盐酸 作用下， 以 异丙醇 为溶剂， 以89%的产率得到N-(2-氯-5-甲氧基苯基)-6-甲氧基
  参考文献：
  名称：

  Discovery of a New Class of Anilinoquinazoline Inhibitors with High Affinity and Specificity for the Tyrosine Kinase Domain of c-Src

  摘要：

  Deregulated activity of the nonreceptor tyrosine kinase c-Src is believed to result in signal transduction, cytoskeletal and adhesion changes, ultimately promoting a tumor-invasive phenotype. We report here the discovery of a new class of anilinoquinazoline inhibitors with high affinity and specificity for the tyrosine kinase domain of the c-Src enzyme. Special attention was directed toward finding inhibitors selective against KDR tyrosine kinase in order to ensure that the in vivo profile of a specific Src inhibitor could be determined. The 4-aminobenzodioxole quinazoline series gave compounds with excellent potency and selectivity. The most interesting compounds were evaluated in vivo and displayed good pharmacokinetics following oral dosing. Compounds such as the aminobenzodioxoles were shown to be potent inhibitors of tumor growth in a c-Src-transformed 3T3 xenograft model in vivo, resulting in more than 90% growth inhibition at doses as low as 6 mg/kg po once daily. Src tyrosine kinase inhibitors such as these may provide a novel therapeutic modality for targeting cancer invasion and metastasis.

  DOI：

  10.1021/jm030317k

文献信息

• TRIAZOLOPYRIMIDINE COMPOUNDS AND USES THEREOF
  申请人：CHAN Ho Man

  公开号：US20160176882A1

  公开（公告）日：2016-06-23

  A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is provided that has been shown to be useful for treating a PRC2-mediated disease or disorder: wherein R 1 , R 2 , R 3 , R 4 , R 5 , and n are as defined herein.

  提供了一种由化合物（I）或其药学上可接受的盐组成的药物，已被证明对治疗PRC2介导的疾病或紊乱有用：其中R1、R2、R3、R4、R5和n的定义如本文所述。
• [EN] IMIDAZOPYRIMIDINE COMPOUNDS USEFUL FOR THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS D'IMIDAZOPYRIMIDINE UTILES POUR LE TRAITEMENT DU CANCER
  申请人：NOVARTIS AG

  公开号：WO2017221100A1

  公开（公告）日：2017-12-28

  A compound of Formula (IA), or a pharmaceutically acceptable salt thereof, is provided that has been shown to be useful for treating a PRC2-mediated disease or disorder: wherein A, R3, R4, R6, and R7 are as defined herein.

  提供了一种具有以下结构式（IA）的化合物，或其药用盐，已被证明对治疗PRC2介导的疾病或紊乱有用：其中A，R3，R4，R6和R7如本文所定义。
• [EN] FORMYLATED N-HETEROCYCLIC DERIVATIVES AS FGFR4 INHIBITORS<br/>[FR] DÉRIVÉS N-HÉTÉROCYCLIQUES FORMYLÉS UTILISÉS EN TANT QU'INHIBITEURS DE FGFR4
  申请人：NOVARTIS AG

  公开号：WO2016151499A1

  公开（公告）日：2016-09-29

  The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; (I) a method for manufacturing said compound, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition comprising said compound.

  本发明提供了化合物(I)或其药学上可接受的盐；(I)制造该化合物的方法及其治疗用途。本发明还提供了药理活性剂的组合物和包含该化合物的药物组合物。
• [EN] TRIAZOLOPYRIDINE COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS DE TRIAZOLOPYRIDINE ET LEURS UTILISATIONS
  申请人：NOVARTIS AG

  公开号：WO2017221092A1

  公开（公告）日：2017-12-28

  A compound of Formula (IA), or a pharmaceutically acceptable salt thereof, is provided that has been shown to be useful for treating a PRC2-mediated disease or disorder: wherein A, R6, R7 and R8 are as defined herein.

  提供了一种具有公式（IA）的化合物，或其药用可接受的盐，已被证明可用于治疗PRC2介导的疾病或紊乱：其中A，R6，R7和R8如本文所定义。
• [EN] QUINAZOLINE DERIVATIVES<br/>[FR] DERIVES QUINAZOLINIQUES
  申请人：ASTRAZENECA AB

  公开号：WO2002092577A1

  公开（公告）日：2002-11-21

  The invention concerns quinazoline derivatives of Formula (I), wherein each of R?1, R2 and R3¿ have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an anti-invasive agent in the containment and/or treatment of solid tumour disease.

  该发明涉及公式（I）的喹唑啉衍生物，其中R1、R2和R3中的每一个具有在说明书中定义的任何含义；制备它们的过程，包含它们的制药组合物以及它们在制造用于抗侵袭剂的药物治疗固体肿瘤疾病中的使用。