N'-(2,3-dihydrobenzofuran-7-yl)-N-(3-methylsulfonylphenyl)pyrimidine-2,4-diamine | 945396-42-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N'-(2,3-dihydrobenzofuran-7-yl)-N-(3-methylsulfonylphenyl)pyrimidine-2,4-diamine
• 英文别名: N4-(2,3-dihydrobenzofuran-7-yl)-N2-(3-(methylsulfonyl)phenyl)pyrimidine-2,4-diamine；4-N-(2,3-dihydro-1-benzofuran-7-yl)-2-N-(3-methylsulfonylphenyl)pyrimidine-2,4-diamine
• CAS: 945396-42-9
• 化学式: C₁₉H₁₈N₄O₃S
• 分子量: 382.443
• InChiKey: QAUBUHQKFKUNIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氯-N-[3-(甲基磺酰基)苯基]-2-嘧啶胺 、 2,3-二氢苯并[b]呋喃-7-胺 在 盐酸 作用下， 以 异丙醇 为溶剂， 生成 N'-(2,3-dihydrobenzofuran-7-yl)-N-(3-methylsulfonylphenyl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Inhibitors of the tyrosine kinase EphB4. Part 3: Identification of non-benzodioxole-based kinase inhibitors

  摘要：

  Starting from the initial bis-anilinopyrimidine 1, good potency against EphB4 was retained when benzodioxole at C-4 was replaced by an indazole. The key interactions of the indazole with the protein were characterised by crystallographic studies. Further optimisation led to compound 20, a potent inhibitor of the EphB4 and Src kinases with good pharmacokinetics in various preclinical species and high fraction unbound in plasma. Compound 20 may be used as a tool for evaluating the potential of EphB4 kinase inhibitors in vivo.

  DOI：

  10.1016/j.bmcl.2010.08.100

文献信息

• PYRIMIDINE DERIVATIVES
  申请人：Kettle Jason Grant

  公开号：US20110046108A1

  公开（公告）日：2011-02-24

  The invention concerns benzamide compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R 1 , ring A, n, R 3 , and R 4 are as defined in the description. The present invention also relates to processes for the preparation of such compounds, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours or other proliferative conditions which are sensitive to the inhibition of EphB4, and/or EphA2 and/or Src kinases.

  这项发明涉及Formula (I)的苯甲酰胺化合物或其药用可接受的盐，其中R1、环A、n、R3和R4如描述中所定义。本发明还涉及制备这种化合物的方法、含有它们的药物组合物以及它们在制造用作抗增殖剂的药物中的用途，用于预防或治疗对EphB4、EphA2和/或Src激酶抑制敏感的肿瘤或其他增殖病症。
• Inhibitors of the tyrosine kinase EphB4. Part 3: Identification of non-benzodioxole-based kinase inhibitors
  作者：Catherine Bardelle、Bernard Barlaam、Nigel Brooks、Tanya Coleman、Darren Cross、Richard Ducray、Isabelle Green、Christine Lambert-van der Brempt、Annie Olivier、Jon Read

  DOI：10.1016/j.bmcl.2010.08.100

  日期：2010.11

  Starting from the initial bis-anilinopyrimidine 1, good potency against EphB4 was retained when benzodioxole at C-4 was replaced by an indazole. The key interactions of the indazole with the protein were characterised by crystallographic studies. Further optimisation led to compound 20, a potent inhibitor of the EphB4 and Src kinases with good pharmacokinetics in various preclinical species and high fraction unbound in plasma. Compound 20 may be used as a tool for evaluating the potential of EphB4 kinase inhibitors in vivo.