N,N-dimethyl-N'-[5-oxo-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]sulfuric diamide | 1309961-00-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N,N-dimethyl-N'-[5-oxo-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]sulfuric diamide
• CAS: 1309961-00-9
• 化学式: C₂₂H₂₆BN₃O₅S
• 分子量: 455.343
• InChiKey: CEBPKRMBYWPBLF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.27
• 重原子数：
  32.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  97.83
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  1-(2-fluoro-3-pyrrolidin-1-ylpropyl)-4-iodo-1H-pyrazole 、 N,N-dimethyl-N'-[5-oxo-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]sulfuric diamide 在 potassium fluoride 、 tris-(dibenzylideneacetone)dipalladium(0) 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以28%的产率得到N'-(3-{1-[2-fluoro-3-(pyrrolidin-1-yl)propyl]-1H-pyrazol-4-yl}-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-N,N-dimethylsulfuric diamide
  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
• 作为产物：
  描述：

  5-氯-2-甲基-3-吡啶羧酸甲酯 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium tert-butylate 、 potassium acetate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三环己基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 为溶剂， 反应 2.0h， 生成 N,N-dimethyl-N'-[5-oxo-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]sulfuric diamide
  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