N-(2-chloro-5-(4-(pyridin-4-yl)thieno[2,3-d]pyrimidin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide

• 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-(2-chloro-5-(4-(pyridin-4-yl)thieno[2,3-d]pyrimidin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide
• 英文别名: N-[2-chloro-5-(4-pyridin-4-ylthieno[2,3-d]pyrimidin-6-yl)pyridin-3-yl]-4-fluorobenzenesulfonamide
• 化学式: C₂₂H₁₃ClFN₅O₂S₂
• 分子量: 497.961
• InChiKey: ALNQLISVOLPLER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  134
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  6-溴-4-氯噻吩[2,3-D]嘧啶 在 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 potassium carbonate 、 联硼酸频那醇酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 48.5h， 生成 N-(2-chloro-5-(4-(pyridin-4-yl)thieno[2,3-d]pyrimidin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide
  参考文献：
  名称：

  Discovery of a Novel Series of Thienopyrimidine as Highly Potent and Selective PI3K Inhibitors

  摘要：

  Inhibition of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway provides a promising new approach for cancer therapy. Through a rational design, a novel series of thienopyrimidine was discovered as highly potent and selective PI3K inhibitors. These thienopyrimidine derivatives were demonstrated to bear nanomolar PI3K alpha inhibitory potency with over 100-fold selectivity against mTOR kinase. The lead compounds 6g and 6k showed good developability profiles in cell-based proliferation and ADME assays. In this communication, their design, synthesis, structure activity relationship, selectivity, and some developability properties are described.

  DOI：

  10.1021/ml5005014

文献信息

• Discovery of a Novel Series of Thienopyrimidine as Highly Potent and Selective PI3K Inhibitors
  作者：Fangbin Han、Songwen Lin、Peng Liu、Xiujie Liu、Jing Tao、Xiaobing Deng、Chongqin Yi、Heng Xu

  DOI：10.1021/ml5005014

  日期：2015.4.9

  Inhibition of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway provides a promising new approach for cancer therapy. Through a rational design, a novel series of thienopyrimidine was discovered as highly potent and selective PI3K inhibitors. These thienopyrimidine derivatives were demonstrated to bear nanomolar PI3K alpha inhibitory potency with over 100-fold selectivity against mTOR kinase. The lead compounds 6g and 6k showed good developability profiles in cell-based proliferation and ADME assays. In this communication, their design, synthesis, structure activity relationship, selectivity, and some developability properties are described.