N-methyl-N'-[3-(4-methylpiperazin-1-ylmethyl)phenyl]pyrimidine-4,6-diamine | 943189-22-8

• 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-methyl-N'-[3-(4-methylpiperazin-1-ylmethyl)phenyl]pyrimidine-4,6-diamine
• 英文别名: N-methyl-N'-[3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-pyrimidine-4,6-diamine；6-N-methyl-4-N-[3-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrimidine-4,6-diamine
• CAS: 943189-22-8
• 化学式: C₁₇H₂₄N₆
• 分子量: 312.418
• InChiKey: VMKSNLMLSPRQKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  56.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,4-dichloro-3-isocyanato-1,5-dimethoxybenzene 、 N-methyl-N'-[3-(4-methylpiperazin-1-ylmethyl)phenyl]pyrimidine-4,6-diamine 以 甲苯 为溶剂， 反应 3.0h， 以33%的产率得到3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methyl-1-{6-[3-(4-methylpiperazin-1-ylmethyl)phenylamino]pyrimidin-4-yl}urea
  参考文献：
  名称：

  Discovery of 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), A Potent and Selective Inhibitor of the Fibroblast Growth Factor Receptor Family of Receptor Tyrosine Kinase

  摘要：

  A novel series of N-aryl-N'-pyrimidin-4-yl ureas has been optimized to afford potent and selective inhibitors of the fibroblast growth factor receptor tyrosine kinases 1, 2, and 3 by rationally designing the substitution pattern of the aryl ring. On the basis of its in vitro profile, compound 1h (NVP-BGJ398) was selected for in vivo evaluation and showed significant antitumor activity in RT112 bladder cancer xenografts models overexpressing wild-type FGFR3. These results support the potential therapeutic use of 1h as a new anticancer agent.

  DOI：

  10.1021/jm2006222
• 作为产物：
  描述：

  间硝基氯化苄 在 盐酸 、 氢气 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 丙酮 为溶剂， 反应 37.5h， 生成 N-methyl-N'-[3-(4-methylpiperazin-1-ylmethyl)phenyl]pyrimidine-4,6-diamine
  参考文献：
  名称：

  Discovery of 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), A Potent and Selective Inhibitor of the Fibroblast Growth Factor Receptor Family of Receptor Tyrosine Kinase

  摘要：

  A novel series of N-aryl-N'-pyrimidin-4-yl ureas has been optimized to afford potent and selective inhibitors of the fibroblast growth factor receptor tyrosine kinases 1, 2, and 3 by rationally designing the substitution pattern of the aryl ring. On the basis of its in vitro profile, compound 1h (NVP-BGJ398) was selected for in vivo evaluation and showed significant antitumor activity in RT112 bladder cancer xenografts models overexpressing wild-type FGFR3. These results support the potential therapeutic use of 1h as a new anticancer agent.

  DOI：

  10.1021/jm2006222

文献信息

• Pyrimidinyl Aryl Urea Derivatives Being Fgf Inhibitors
  申请人：Bold Guido

  公开号：US20080312248A1

  公开（公告）日：2008-12-18

  The invention relates to heteroaryl aryl ureas of the formula IA, wherein the radicals and symbols have the meanings as defined herein, the use of such compounds in the treatment of protein kinase dependent diseases; to pharmaceutical preparations comprising said heteroaryl aryl ureas, to processes for the manufacture of such novel compounds and to methods of treatment comprising the use of such heteroaryl aryl ureas.

  本发明涉及公式IA的杂环芳基基脲化合物，其中基团和符号的含义如本文所定义，这些化合物在蛋白激酶依赖性疾病的治疗中的使用；含有上述杂环芳基基脲化合物的制药制剂；制备这些新化合物的方法以及使用这些杂环芳基基脲化合物的治疗方法。
• Pyrimidinyl aryl urea derivatives being FGF inhibitors
  申请人：Novartis AG

  公开号：US08293746B2

  公开（公告）日：2012-10-23

  The invention relates to heteroaryl aryl ureas of the formula IA, wherein the radicals and symbols have the meanings as defined herein, the use of such compounds in the treatment of protein kinase dependent diseases; to pharmaceutical preparations comprising said heteroaryl aryl ureas, to processes for the manufacture of such novel compounds and to methods of treatment comprising the use of such heteroaryl aryl ureas.

  本发明涉及公式IA的杂环芳基基脲，其中基团和符号的含义如此处所定义，以及在蛋白激酶依赖性疾病治疗中使用这种化合物；包括含有这种杂环芳基基脲的制药制剂，制造这种新化合物的工艺以及使用这种杂环芳基基脲的治疗方法。
• Pyrimidinyl Aryl Urea Derivatives being FGF Inhibitors
  申请人：Novartis AG

  公开号：US20130030171A1

  公开（公告）日：2013-01-31

  The invention relates to heteroaryl aryl ureas of the formula IA, wherein the radicals and symbols have the meanings as defined herein, the use of such compounds in the treatment of protein kinase dependent diseases; to pharmaceutical preparations comprising said heteroaryl aryl ureas, to processes for the manufacture of such novel compounds and to methods of treatment comprising the use of such heteroaryl aryl ureas.

  本发明涉及式子IA的杂环芳基芳基脲，其中基团和符号的含义在此定义，这些化合物在蛋白激酶依赖性疾病的治疗中的使用；制备包括所述杂环芳基芳基脲的药物制剂；制造这种新型化合物的过程以及包括使用这种杂环芳基芳基脲的治疗方法。
• Pyrirnidinyl aryl urea derivatives being FGF inhibitors
  申请人：Novartis AG

  公开号：US08759517B2

  公开（公告）日：2014-06-24

  The invention relates to heteroaryl aryl ureas of the formula IA, wherein the radicals and symbols have the meanings as defined herein, the use of such compounds in the treatment of protein kinase dependent diseases; to pharmaceutical preparations comprising said heteroaryl aryl ureas, to processes for the manufacture of such novel compounds and to methods of treatment comprising the use of such heteroaryl aryl ureas.

  本发明涉及公式IA的杂环芳基基脲化合物，其中基团和符号的含义如本文所定义，在蛋白激酶依赖性疾病的治疗中使用这种化合物；包括含有这些杂环芳基基脲化合物的制药制剂，制造这种新型化合物的方法和使用这种杂环芳基基脲化合物的治疗方法。
• WO2007/71752
  申请人：——

  公开号：——

  公开（公告）日：——