N-(6-(5-(5-chlorothiophene-2-sulfonamido)-6-methoxypyridin-3-yl)-4-methylthieno[2,3-d]pyrimidin-2-yl)acetamide

• 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: N-(6-(5-(5-chlorothiophene-2-sulfonamido)-6-methoxypyridin-3-yl)-4-methylthieno[2,3-d]pyrimidin-2-yl)acetamide
• 英文别名: N-[6-[5-[(5-chlorothiophen-2-yl)sulfonylamino]-6-methoxypyridin-3-yl]-4-methylthieno[2,3-d]pyrimidin-2-yl]acetamide
• 化学式: C₁₉H₁₆ClN₅O₄S₃
• 分子量: 510.018
• InChiKey: AUQPVAKLJJBNFN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  188
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3-氨基-5-溴-2-甲氧基吡啶 在 吡啶 、 4-二甲氨基吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 8.0h， 生成 N-(6-(5-(5-chlorothiophene-2-sulfonamido)-6-methoxypyridin-3-yl)-4-methylthieno[2,3-d]pyrimidin-2-yl)acetamide
  参考文献：
  名称：

  Discovery of new thienopyrimidine derivatives as potent and orally efficacious phosphoinositide 3-kinase inhibitors

  摘要：

  A series of new thienopyrimidine derivatives has been discovered as potent PI3K inhibitors. The systematic SAR studies for these analogues are described. Among them, 8a and 9a exhibit nanomolar enzymatic potencies and sub-micromolar cellular anti-proliferative activities. 8a displays favorable pharmacokinetic profiles, while 9a easily undergoes deacetylation to yield a major metabolite 8a. Furthermore, 8a and 9a potently inhibit tumor growth in a dose-dependent manner in the NCI-H460 xenograft model with an acceptable safety profile. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.12.025

文献信息

• Discovery of new thienopyrimidine derivatives as potent and orally efficacious phosphoinositide 3-kinase inhibitors
  作者：Songwen Lin、Chunyang Wang、Ming Ji、Deyu Wu、Yuanhao Lv、Li Sheng、Fangbin Han、Yi Dong、Kehui Zhang、Yakun Yang、Yan Li、Xiaoguang Chen、Heng Xu

  DOI：10.1016/j.bmc.2017.12.025

  日期：2018.2

  A series of new thienopyrimidine derivatives has been discovered as potent PI3K inhibitors. The systematic SAR studies for these analogues are described. Among them, 8a and 9a exhibit nanomolar enzymatic potencies and sub-micromolar cellular anti-proliferative activities. 8a displays favorable pharmacokinetic profiles, while 9a easily undergoes deacetylation to yield a major metabolite 8a. Furthermore, 8a and 9a potently inhibit tumor growth in a dose-dependent manner in the NCI-H460 xenograft model with an acceptable safety profile. (C) 2017 Elsevier Ltd. All rights reserved.