N-(5-oxo-3-phenyl-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-8-yl)methanesulfonamide | 1350475-62-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-(5-oxo-3-phenyl-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-8-yl)methanesulfonamide
• 英文别名: N-(2-oxo-5-phenyl-7-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-13-yl)methanesulfonamide
• CAS: 1350475-62-5
• 化学式: C₂₁H₁₆N₂O₃S
• 分子量: 376.436
• InChiKey: CPNJMBOSJCJHHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  84.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  间溴苯甲醛 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium tert-butylate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 为溶剂， 生成 N-(5-oxo-3-phenyl-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-8-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

• Discovery of a 5<i>H</i>-Benzo[4,5]cyclohepta[1,2-<i>b</i>]pyridin-5-one (MK-2461) Inhibitor of c-Met Kinase for the Treatment of Cancer
  作者：Jason D. Katz、James P. Jewell、David J. Guerin、Jongwon Lim、Christopher J. Dinsmore、Sujal V. Deshmukh、Bo-Sheng Pan、C. Gary Marshall、Wei Lu、Michael D. Altman、William K. Dahlberg、Lenora Davis、Danielle Falcone、Ana E. Gabarda、Gaozhen Hang、Harold Hatch、Rachael Holmes、Kaiko Kunii、Kevin J. Lumb、Bart Lutterbach、Robert Mathvink、Naim Nazef、Sangita B. Patel、Xianlu Qu、John F. Reilly、Keith W. Rickert、Craig Rosenstein、Stephen M. Soisson、Kerrie B. Spencer、Alexander A. Szewczak、Deborah Walker、Wenxian Wang、Jonathan Young、Qinwen Zeng

  DOI：10.1021/jm200112k

  日期：2011.6.23

  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.