1-(5-Chloro-2-methylphenyl)-3-(3-(8-(pyridin-4-ylmethylamino)imidazo[1,2-a]pyrazin-6-yl)phenyl)urea | 1202810-85-2

• 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: 1-(5-Chloro-2-methylphenyl)-3-(3-(8-(pyridin-4-ylmethylamino)imidazo[1,2-a]pyrazin-6-yl)phenyl)urea
• 英文别名: 1-(5-chloro-2-methylphenyl)-3-[3-[8-(pyridin-4-ylmethylamino)imidazo[1,2-a]pyrazin-6-yl]phenyl]urea
• CAS: 1202810-85-2
• 化学式: C₂₆H₂₂ClN₇O
• 分子量: 483.96
• InChiKey: JHUWWAUVQCEKHO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  96.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-(3-aminophenyl)-N-(pyridin-4-ylmethyl)imidazo[1,2-a]pyrazin-8-amine 、 5-氯-2-甲基苯基异氰酸酯 以 甲苯 为溶剂， 反应 0.5h， 生成 1-(5-Chloro-2-methylphenyl)-3-(3-(8-(pyridin-4-ylmethylamino)imidazo[1,2-a]pyrazin-6-yl)phenyl)urea
  参考文献：
  名称：

  Imidazo[1,2-a]pyrazine diaryl ureas: Inhibitors of the receptor tyrosine kinase EphB4

  摘要：

  Inhibition of receptor tyrosine kinases (RTKs) such as vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs) has been validated by recently launched small molecules Sutent(R) and Nexavar(R), both of which display activities against several angiogenesis-related RTKs. EphB4, a receptor tyrosine kinase (RTK) involved in the processes of embryogenesis and angiogenesis, has been shown to be aberrantly up regulated in many cancer types such as breast, lung, bladder and prostate. We propose that inhibition of EphB4 in addition to other validated RTKs would enhance the anti-angiogenic effect and ultimately result in more pronounced anti-cancer efficacy. Herein we report the discovery and SAR of a novel series of imidazo[1,2-a]pyrazine diarylureas that show nano-molar potency for the EphB4 receptor, in addition to potent activity against several other RTKs. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.037

文献信息

• Imidazo[1,2-a]pyrazine diaryl ureas: Inhibitors of the receptor tyrosine kinase EphB4
  作者：Scott A. Mitchell、Mihaela Diana Danca、Peter A. Blomgren、James W. Darrow、Kevin S. Currie、Jeffrey E. Kropf、Seung H. Lee、Steven L. Gallion、Jin-Ming Xiong、Douglas A. Pippin、Robert W. DeSimone、David R. Brittelli、David C. Eustice、Aaron Bourret、Melissa Hill-Drzewi、Patricia M. Maciejewski、Lisa L. Elkin

  DOI：10.1016/j.bmcl.2009.10.037

  日期：2009.12

  Inhibition of receptor tyrosine kinases (RTKs) such as vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs) has been validated by recently launched small molecules Sutent(R) and Nexavar(R), both of which display activities against several angiogenesis-related RTKs. EphB4, a receptor tyrosine kinase (RTK) involved in the processes of embryogenesis and angiogenesis, has been shown to be aberrantly up regulated in many cancer types such as breast, lung, bladder and prostate. We propose that inhibition of EphB4 in addition to other validated RTKs would enhance the anti-angiogenic effect and ultimately result in more pronounced anti-cancer efficacy. Herein we report the discovery and SAR of a novel series of imidazo[1,2-a]pyrazine diarylureas that show nano-molar potency for the EphB4 receptor, in addition to potent activity against several other RTKs. (C) 2009 Elsevier Ltd. All rights reserved.