N-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-N-(2,4-dimethoxybenzyl)-2-(1H-imidazol-1-yl)ethanesulfonamide | 1309960-90-4

• 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-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-N-(2,4-dimethoxybenzyl)-2-(1H-imidazol-1-yl)ethanesulfonamide
• CAS: 1309960-90-4
• 化学式: C₂₈H₂₅ClN₄O₅S
• 分子量: 565.049
• InChiKey: CLTMWSFVQGRKOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.65
• 重原子数：
  39.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  103.62
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  N-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-N-(2,4-dimethoxybenzyl)-2-(1H-imidazol-1-yl)ethanesulfonamide 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 以300 mg的产率得到N-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-2-(1H-imidazol-1-yl)ethanesulfonamide
  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 N-甲基吗啉 、 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium tert-butylate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 生成 N-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-N-(2,4-dimethoxybenzyl)-2-(1H-imidazol-1-yl)ethanesulfonamide
  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