N-(3-phenyl-5-pyrrolidin-1-yl-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)methanesulfonamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并环庚烷吡啶
• 英文名称: N-(3-phenyl-5-pyrrolidin-1-yl-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)methanesulfonamide
• 英文别名: N-(5-phenyl-2-pyrrolidin-1-yl-7-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-14-yl)methanesulfonamide
• 化学式: C₂₅H₂₅N₃O₂S
• 分子量: 431.558
• InChiKey: AAPKMLWLODKOBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  70.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  7-bromo-3-phenyl-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one 在 sodium tetrahydroborate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 氯化亚砜 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 N-(3-phenyl-5-pyrrolidin-1-yl-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)methanesulfonamide
  参考文献：
  名称：

  Discovery of a 5H-Benzo[4,5]cyclohepta[1,2-b]pyridin-5-one (MK-2461) Inhibitor of c-Met Kinase for the Treatment of Cancer

  摘要：

  c-Met is a transmembrane tyrosine kinase that mediates activation of several signaling pathways implicated in aggressive cancer phenotypes. In recent years, research into this area has highlighted c-Met as an attractive cancer drug target, triggering a number of approaches to disrupt aberrant c-Met signaling. Screening efforts identified a unique class of 5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one kinase inhibitors, exemplified by 1. Subsequent SAR studies led to the development of 81 (MK-2461), a potent inhibitor of c-Met that was efficacious in preclinical animal models of tumor suppression. In addition, biochemical studies and X-ray analysis have revealed that this unique class of kinase inhibitors binds preferentially to the activated (phosphorylated) form of the kinase. This report details the development of 81 and provides a description of its unique biochemical properties.

  DOI：

  10.1021/jm200112k

文献信息

• Tyrosine kinase inhibitors
  申请人：Dinsmore J. Christopher

  公开号：US20060293358A1

  公开（公告）日：2006-12-28

  The present invention relates to 5H-benzo[4,5]cyclohepta[1,2-b]pyridine compounds, that are useful for treating cellular proliferative diseases, for treating disorders associated with MET activity, and for inhibiting the receptor tyrosine kinase MET. The invention also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.

  本发明涉及5H-苯并[4,5]环庚[1,2-b]吡啶化合物，用于治疗细胞增殖性疾病，治疗与MET活性相关的疾病，以及抑制受体酪氨酸激酶MET。该发明还涉及包含这些化合物的组合物，以及利用它们治疗哺乳动物癌症的方法。
• Benzocycloheptapyridines as inhibitors of the receptor tyrosine kinase MET
  申请人：Merck Sharp & Dohme Corp.

  公开号：US08207186B2

  公开（公告）日：2012-06-26

  The present invention relates to 5H-benzo[4,5]cyclohepta[1,2-b]pyridine compounds, that are useful for treating cellular proliferative diseases, for treating disorders associated with MET activity, and for inhibiting the receptor tyrosine kinase MET. The invention also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.

  本发明涉及5H-苯并[4,5]环庚[1,2-b]吡啶化合物，用于治疗细胞增殖性疾病，治疗与MET活性相关的疾病，以及抑制受体酪氨酸激酶MET。本发明还涉及包含这些化合物的组合物和使用它们治疗哺乳动物癌症的方法。
• Benzocycloheptapyridines as inhibitors of the receptor tyrosine kinase met
  申请人：Dinsmore Christopher J.

  公开号：US20090197908A1

  公开（公告）日：2009-08-06

  The present invention relates to 5H-benzo[4,5]cyclohepta[1,2-b]pyridine compounds, that are useful for treating cellular proliferative diseases, for treating disorders associated with MET activity, and for inhibiting the receptor tyrosine kinase MET. The invention also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.

  本发明涉及用于治疗细胞增殖性疾病、治疗与MET活性相关的疾病以及抑制受体酪氨酸激酶MET的5H-苯并[4,5]环庚[1,2-b]吡啶化合物。本发明还涉及包含这些化合物的组合物以及使用它们治疗哺乳动物癌症的方法。
• BENZOCYCLOHEPTAPYRIDINES AS INHIBITORS OF THE RECEPTOR TYROSINE KINASE MET
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1896421B1

  公开（公告）日：2011-09-14
• US7550478B2
  申请人：——

  公开号：US7550478B2

  公开（公告）日：2009-06-23