1-(3-(tert-butyl)-1-(3-((2-ethoxyethyl)amino)phenyl)-1H-pyrazol-5-yl)-3-(4-(2-morpholinoethoxy)naphthalen-1-yl)urea | 1609257-17-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(3-(tert-butyl)-1-(3-((2-ethoxyethyl)amino)phenyl)-1H-pyrazol-5-yl)-3-(4-(2-morpholinoethoxy)naphthalen-1-yl)urea
• 英文别名: 1-[5-Tert-butyl-2-[3-(2-ethoxyethylamino)phenyl]pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea；1-[5-tert-butyl-2-[3-(2-ethoxyethylamino)phenyl]pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea
• CAS: 1609257-17-1
• 化学式: C₃₄H₄₄N₆O₄
• 分子量: 600.761
• InChiKey: GITDAMOZKGMYFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2,2,2-trichloroethyl 3-t-butyl-1-(3-nitrophenyl)-1H-pyrazol-5-ylcarbamate 在 5%-palladium/activated carbon 、 甲酸铵 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.67h， 生成 1-(3-(tert-butyl)-1-(3-((2-ethoxyethyl)amino)phenyl)-1H-pyrazol-5-yl)-3-(4-(2-morpholinoethoxy)naphthalen-1-yl)urea
  参考文献：
  名称：

  Identification of Type II and III DDR2 Inhibitors

  摘要：

  Discoidin domain-containing receptors (DDRs) exhibit a unique mechanism of action among the receptor tyrosine kinases (RTKs) because their catalytic activity is induced by extracellular collagen binding. Moreover, they are essential components in the assimilation of extracellular signals. Recently, DDRs were reported to be significantly linked to tumor progression in breast cancer by facilitating the processes of invasion, migration, and metastasis. Here, we report the successful development of a fluorescence-based, direct binding assay for the detection of type II and III DFG-out binders for DDR2. Using sequence alignments and homology modeling, we designed a DDR2 construct appropriate for fluorescent labeling. Successful assay development was validated by sensitive detection of a reference DFG-out binder. Subsequent downscaling led to convenient application to high-throughput screening formats. Screening of a representative compound library identified high-affinity DDR2 ligands validated by orthogonal activity-based assays, and a subset of identified compounds was further investigated with respect to DDR1 inhibition.

  DOI：

  10.1021/jm500167q

文献信息

• Identification of Type II and III DDR2 Inhibitors
  作者：André Richters、Hoang D. Nguyen、Trang Phan、Jeffrey R. Simard、Christian Grütter、Julian Engel、Daniel Rauh

  DOI：10.1021/jm500167q

  日期：2014.5.22

  Discoidin domain-containing receptors (DDRs) exhibit a unique mechanism of action among the receptor tyrosine kinases (RTKs) because their catalytic activity is induced by extracellular collagen binding. Moreover, they are essential components in the assimilation of extracellular signals. Recently, DDRs were reported to be significantly linked to tumor progression in breast cancer by facilitating the processes of invasion, migration, and metastasis. Here, we report the successful development of a fluorescence-based, direct binding assay for the detection of type II and III DFG-out binders for DDR2. Using sequence alignments and homology modeling, we designed a DDR2 construct appropriate for fluorescent labeling. Successful assay development was validated by sensitive detection of a reference DFG-out binder. Subsequent downscaling led to convenient application to high-throughput screening formats. Screening of a representative compound library identified high-affinity DDR2 ligands validated by orthogonal activity-based assays, and a subset of identified compounds was further investigated with respect to DDR1 inhibition.