N-((5-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)(phenyl)methyl)-3-(methylthio)propanamide | 1061610-83-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-((5-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)(phenyl)methyl)-3-(methylthio)propanamide
• 英文别名: N-[(5-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]-3-fluorophenyl}-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)(phenyl)methyl]-3-(methylsulfanyl)propanamide；N-[[5-[4-(6,7-dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]-1-methyl-6-oxopyrimidin-2-yl]-phenylmethyl]-3-methylsulfanylpropanamide
• CAS: 1061610-83-0
• 化学式: C₃₃H₃₁FN₄O₅S
• 分子量: 614.697
• InChiKey: UGUJTUUACHEEGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-(amino(phenyl)methyl)-5-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-3-methylpyrimidin-4(3H)-one 、 3-甲硫基丙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以47%的产率得到N-((5-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)(phenyl)methyl)-3-(methylthio)propanamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Potent c-Met Inhibitors

  摘要：

  c-Met is a receptor tyrosine kinase that plays a key role in several cellular processes but has also been found to be overexpressed and mutated in different human cancers. Consequently, targeting this enzyme has become an area of intense research in drug discovery. Our studies began with the design and synthesis of novel pyrimidone 7, which was found to be a potent c-Met inhibitor. Subsequent SAR studies identified 22 as a more potent analog, whereas an X-ray crystal structure of 7 bound to c-Met revealed an unexpected binding conformation. This latter finding led to the development of a new series that featured compounds that were more potent both in vitro and in vivo than 22 and also exhibited different binding conformations to c-Met. Novel c-Met inhibitors have been designed, developed, and found to be potent in vitro and in vivo.

  DOI：

  10.1021/jm8006189

文献信息

• QUINOLINES AND QUINAZOLINE ANALOGS AND THEIR USE AS MEDICAMENTS FOR TREATING CANCER
  申请人：Amgen Inc.

  公开号：EP1827434B1

  公开（公告）日：2014-01-15
• Design, Synthesis, and Biological Evaluation of Potent c-Met Inhibitors
  作者：Noel D. D’Angelo、Steven F. Bellon、Shon K. Booker、Yuan Cheng、Angela Coxon、Celia Dominguez、Ingrid Fellows、Douglas Hoffman、Randall Hungate、Paula Kaplan-Lefko、Matthew R. Lee、Chun Li、Longbin Liu、Elizabeth Rainbeau、Paul J. Reider、Karen Rex、Aaron Siegmund、Yaxiong Sun、Andrew S. Tasker、Ning Xi、Shimin Xu、Yajing Yang、Yihong Zhang、Teresa L. Burgess、Isabelle Dussault、Tae-Seong Kim

  DOI：10.1021/jm8006189

  日期：2008.9.25

  c-Met is a receptor tyrosine kinase that plays a key role in several cellular processes but has also been found to be overexpressed and mutated in different human cancers. Consequently, targeting this enzyme has become an area of intense research in drug discovery. Our studies began with the design and synthesis of novel pyrimidone 7, which was found to be a potent c-Met inhibitor. Subsequent SAR studies identified 22 as a more potent analog, whereas an X-ray crystal structure of 7 bound to c-Met revealed an unexpected binding conformation. This latter finding led to the development of a new series that featured compounds that were more potent both in vitro and in vivo than 22 and also exhibited different binding conformations to c-Met. Novel c-Met inhibitors have been designed, developed, and found to be potent in vitro and in vivo.