5-(3-fluoro-4-methoxyphenyl)-3-methyl-2-(methylthio)pyrimidin-4(3H)-one | 890021-30-4

• 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: 5-(3-fluoro-4-methoxyphenyl)-3-methyl-2-(methylthio)pyrimidin-4(3H)-one
• 英文别名: 5-(3-fluoro-4-methoxyphenyl)-3-methyl-2-methylthio-3H-pyrimidin-4-one；5-(3-fluoro-4-methoxyphenyl)-3-methyl-2-methylsulfanylpyrimidin-4-one
• CAS: 890021-30-4
• 化学式: C₁₃H₁₃FN₂O₂S
• 分子量: 280.323
• InChiKey: LNLNUIZEAIJODM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  67.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(3-fluoro-4-methoxyphenyl)-3-methyl-2-(methylthio)pyrimidin-4(3H)-one 在 氢溴酸 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 3.0h， 以100%的产率得到5-(3-fluoro-4-hydroxyphenyl)-3-methyl-2-(methylthio)pyrimidin-4(3H)-one
  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
• 作为产物：
  描述：

  2-甲基硫代-3-甲基嘧啶-4(3h)-酮 、 3-氟-4-甲氧基苯硼酸 在 2-双环己基膦-2',6'-二甲氧基联苯 、 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 作用下， 以 甲苯 为溶剂， 反应 6.25h， 生成 5-(3-fluoro-4-methoxyphenyl)-3-methyl-2-(methylthio)pyrimidin-4(3H)-one
  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

• Substituted heterocycles and methods of use
  申请人：Kim Tae-Seong

  公开号：US20060252777A1

  公开（公告）日：2006-11-09

  Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  所选的化合物对于预防和治疗HGF介导的疾病等疾病是有效的。该发明涵盖了新型化合物、类似物、前药和其药学上可接受的盐、药物组合物以及预防和治疗癌症等疾病和其他疾病或病况的方法。本发明还涉及制造这种化合物的过程，以及在这种过程中有用的中间体。
• Bis-aryl kinase inhibitors and method
  申请人：Kim Tae-Seong

  公开号：US20070054903A1

  公开（公告）日：2007-03-08

  Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  所选化合物对于预防和治疗疾病，如HGF介导的疾病具有有效性。该发明涵盖了新颖的化合物、类似物、前药和其药学上可接受的盐、制药组合物以及预防和治疗涉及癌症等疾病和其他病症或情况的方法。该发明还涉及制造这种化合物的过程以及在这些过程中有用的中间体。
• WO2007/5668
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2006/60318
  申请人：——

  公开号：——

  公开（公告）日：——
• 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