5-(5-(benzyloxy)pyridin-2-yl)-3-methyl-2-(methylthio)pyrimidin-4(3H)-one | 1036763-78-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 5-(5-(benzyloxy)pyridin-2-yl)-3-methyl-2-(methylthio)pyrimidin-4(3H)-one
• 英文别名: 3-methyl-2-methylsulfanyl-5-(5-phenylmethoxypyridin-2-yl)pyrimidin-4-one
• CAS: 1036763-78-6
• 化学式: C₁₈H₁₇N₃O₂S
• 分子量: 339.418
• InChiKey: QBWWXBLHXUYZAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  80.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(5-(benzyloxy)pyridin-2-yl)-3-methyl-2-(methylthio)pyrimidin-4(3H)-one 、 4-氟苯胺 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 168.0h， 生成
  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 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 5-(5-(benzyloxy)pyridin-2-yl)-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：Bellon Steven

  公开号：US20080214544A1

  公开（公告）日：2008-09-04

  Selected compounds are effective for prophylaxis and treatment of diseases, such as c-met mediated diseases and/or 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c-met介导的疾病和/或HGF介导的疾病有效。本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涉及癌症等疾病和其他不适或情况的方法。本发明还涉及制备这些化合物的过程，以及在这些过程中有用的中间体。
• Substituted pyridines and pyrimidines and their use in treatment of cancer
  申请人：Amgen Inc.

  公开号：US07687522B2

  公开（公告）日：2010-03-30

  Selected pyridine and pyrimidine compounds of Formula I are effective for prophylaxis and treatment of diseases, such as c-met mediated diseases and/or 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.

  公式I中选择的吡啶和嘧啶化合物对于预防和治疗c-met介导的疾病和/或HGF介导的疾病有效。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，以及用于预防和治疗涉及癌症等疾病和其他疾病或病症的药物组合物和方法。该发明还涉及制备这种化合物的过程以及在这些过程中有用的中间体。
• SUBSTITUTED HETEROCYCLES AND METHODS OF USE
  申请人：Amgen Inc.

  公开号：EP2125781A2

  公开（公告）日：2009-12-02
• US7687522B2
  申请人：——

  公开号：US7687522B2

  公开（公告）日：2010-03-30
• [EN] SUBSTITUTED HETEROCYCLES AND METHODS OF USE<br/>[FR] HÉTÉROCYCLES SUBSTITUÉS ET LEURS MÉTHODES D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2008079291A2

  公开（公告）日：2008-07-03

  [EN] Selected compounds are effective for prophylaxis and treatment of diseases, such as c-met mediated diseases and/or 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] L'invention concerne des composés sélectionnés qui sont efficace pour la prévention et le traitement de maladies, telles que des maladies induites par c-Met et/ou des maladies induites par HGF. L'invention concerne également de nouveaux composés, des analogues, des promédicaments et leurs sels de qualité pharmaceutique, des compositions pharmaceutiques et des méthodes de prévention et de traitement de maladies et de troubles, y compris le cancer et analogue. La présente invention concerne également des procédés destinés à la fabrication de ces composés et des produits intermédiaires utiles dans ces procédés.