2-(amino(phenyl)methyl)-5-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-3-methylpyrimidin-4(3H)-one | 890019-89-3

• 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: 2-(amino(phenyl)methyl)-5-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-3-methylpyrimidin-4(3H)-one
• 英文别名: 2-(amino-phenyl-methyl)-5-[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluorophenyl]-3-methyl-3H-pyrimidin-4-one；2-[Amino(phenyl)methyl]-5-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]-3-fluorophenyl}-3-methyl-3,4-dihydropyrimidin-4-one；2-[amino(phenyl)methyl]-5-[4-(6,7-dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]-3-methylpyrimidin-4-one
• CAS: 890019-89-3
• 化学式: C₂₉H₂₅FN₄O₄
• 分子量: 512.54
• InChiKey: CFZUQQDNJOFAHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  99.3
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 4.5h， 以31 mg的产率得到2-(amino(phenyl)methyl)-5-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-3-methylpyrimidin-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。
• 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
• US7652009B2
  申请人：——

  公开号：US7652009B2

  公开（公告）日：2010-01-26
• [EN] SUBSTITUTED HETEROCYCLES AND METHODS OF USE<br/>[FR] HETEROCYCLES SUBSTITUES ET LEURS PROCEDES D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2006060318A2

  公开（公告）日：2006-06-08

  [EN] 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.
  [FR] La présente invention a trait à des composés sélectionnés efficaces pour la prévention et le traitement de maladies, telles que des maladies impliquant le facteur de croissance des hépatocytes (HGF). L'invention a également trait à de nouveaux composés, analogues, prodrogues et sels pharmaceutiquement acceptables de ceux-ci, à des compositions pharmaceutiques et à des procédés pour la prévention et le traitement de maladies et d'autres troubles ou conditions comprenant le cancer et analogue. La présente invention a trait en outre à des procédés pour la fabrication de tels composés ainsi qu'à des intermédiaires utiles dans de tels procédés.
• 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.