8-bromo-N-[2-chloro-5-(dimethylcarbamoyl)phenyl]-N-methyl-4,5-dihydrothieno[3,2-d][1]benzoxepine-2-carboxamide | 1365345-71-6

• 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: 8-bromo-N-[2-chloro-5-(dimethylcarbamoyl)phenyl]-N-methyl-4,5-dihydrothieno[3,2-d][1]benzoxepine-2-carboxamide
• CAS: 1365345-71-6
• 化学式: C₂₃H₂₀BrClN₂O₃S
• 分子量: 519.846
• InChiKey: SEPDCOSPJORHOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  78.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-bromo-N-[2-chloro-5-(dimethylcarbamoyl)phenyl]-N-methyl-4,5-dihydrothieno[3,2-d][1]benzoxepine-2-carboxamide 、 甲胺 、 molybdenum hexacarbonyl 在 (acetato-κO)({2-[bis(2-methylphenyl)phosphanyl]phenyl}methyl)palladium 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 为溶剂， 以33%的产率得到methyl 2-(2-chloro-5-(dimethylcarbamoyl)phenylcarbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxylate
  参考文献：
  名称：

  Rational Design of Phosphoinositide 3-Kinase α Inhibitors That Exhibit Selectivity over the Phosphoinositide 3-Kinase β Isoform

  摘要：

  Of the four class I phosphoinositide 3-kinase (PI3K) isoforms, PI3k alpha has justly received the most attention for its potential in cancer therapy. Herein we report our successful approaches to achieve PI3K alpha vs PI3K beta selectivity for two chemical series. In the thienopyrimidine series of inhibitors, we propose that select ligands achieve selectivity derived from a hydrogen bonding interaction with Arg770 of PI3K alpha that is not attained with the corresponding Lys777 of PI3K beta. In the benzoxepin series of inhibitors, the selectivity observed can be rationalized by the difference in electrostatic potential between the two isoforms in a given region rather than any specific interaction.

  DOI：

  10.1021/jm2007084
• 作为产物：
  描述：

  3-氯-4-氨基苯甲酸 在 吡啶 、 氯化亚砜 、 caesium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 8-bromo-N-[2-chloro-5-(dimethylcarbamoyl)phenyl]-N-methyl-4,5-dihydrothieno[3,2-d][1]benzoxepine-2-carboxamide
  参考文献：
  名称：

  Rational Design of Phosphoinositide 3-Kinase α Inhibitors That Exhibit Selectivity over the Phosphoinositide 3-Kinase β Isoform

  摘要：

  Of the four class I phosphoinositide 3-kinase (PI3K) isoforms, PI3k alpha has justly received the most attention for its potential in cancer therapy. Herein we report our successful approaches to achieve PI3K alpha vs PI3K beta selectivity for two chemical series. In the thienopyrimidine series of inhibitors, we propose that select ligands achieve selectivity derived from a hydrogen bonding interaction with Arg770 of PI3K alpha that is not attained with the corresponding Lys777 of PI3K beta. In the benzoxepin series of inhibitors, the selectivity observed can be rationalized by the difference in electrostatic potential between the two isoforms in a given region rather than any specific interaction.

  DOI：

  10.1021/jm2007084

文献信息

• Rational Design of Phosphoinositide 3-Kinase α Inhibitors That Exhibit Selectivity over the Phosphoinositide 3-Kinase β Isoform
  作者：Timothy P. Heffron、BinQing Wei、Alan Olivero、Steven T. Staben、Vickie Tsui、Steven Do、Jennafer Dotson、Adrian J. Folkes、Paul Goldsmith、Richard Goldsmith、Janet Gunzner、John Lesnick、Cristina Lewis、Simon Mathieu、Jim Nonomiya、Stephen Shuttleworth、Daniel P. Sutherlin、Nan Chi Wan、Shumei Wang、Christian Wiesmann、Bing-Yan Zhu

  DOI：10.1021/jm2007084

  日期：2011.11.24

  Of the four class I phosphoinositide 3-kinase (PI3K) isoforms, PI3k alpha has justly received the most attention for its potential in cancer therapy. Herein we report our successful approaches to achieve PI3K alpha vs PI3K beta selectivity for two chemical series. In the thienopyrimidine series of inhibitors, we propose that select ligands achieve selectivity derived from a hydrogen bonding interaction with Arg770 of PI3K alpha that is not attained with the corresponding Lys777 of PI3K beta. In the benzoxepin series of inhibitors, the selectivity observed can be rationalized by the difference in electrostatic potential between the two isoforms in a given region rather than any specific interaction.