1-(4-((2-chloro-4-morpholinothieno[2,3-d]pyrimidin-6-yl)methyl)piperidin-1-yl)-2,2,2-trifluoroethanone | 1346161-38-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 1-(4-((2-chloro-4-morpholinothieno[2,3-d]pyrimidin-6-yl)methyl)piperidin-1-yl)-2,2,2-trifluoroethanone
• 英文别名: 1-[4-[(2-Chloro-4-morpholin-4-ylthieno[2,3-d]pyrimidin-6-yl)methyl]piperidin-1-yl]-2,2,2-trifluoroethanone
• CAS: 1346161-38-3
• 化学式: C₁₈H₂₀ClF₃N₄O₂S
• 分子量: 448.897
• InChiKey: MSHQFBFTWTVSSM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  86.8
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-(4-((2-chloro-4-morpholinothieno[2,3-d]pyrimidin-6-yl)methyl)piperidin-1-yl)-2,2,2-trifluoroethanone 在 borane-dimethyl sulfide complex 、 sodium carbonate 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 0.17h， 生成 5-(4-morpholino-6-((1-(2,2,2-trifluoroethyl)piperidin-4-yl)methyl)thieno[2,3-d]pyrimidin-2-yl)pyrimidin-2-amine
  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：

  2-氯-4-吗啡啉基噻吩并[2,3-D]嘧啶 在 盐酸 、 sodium tetrahydroborate 、 正丁基锂 、 氯化亚砜 、 palladium on activated charcoal 、 氢气 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 solvent 、 二氯甲烷 为溶剂， -78.0~150.0 ℃ 、101.33 kPa 条件下， 反应 21.0h， 生成 1-(4-((2-chloro-4-morpholinothieno[2,3-d]pyrimidin-6-yl)methyl)piperidin-1-yl)-2,2,2-trifluoroethanone
  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.