3-[[(2R)-3,3-dimethylbutan-2-yl]amino]-4-[[2-(pyridin-3-ylamino)pyrimidin-4-yl]amino]cyclobut-3-ene-1,2-dione | 1415548-27-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-[[(2R)-3,3-dimethylbutan-2-yl]amino]-4-[[2-(pyridin-3-ylamino)pyrimidin-4-yl]amino]cyclobut-3-ene-1,2-dione
• CAS: 1415548-27-4
• 化学式: C₁₉H₂₂N₆O₂
• 分子量: 366.423
• InChiKey: JYFUPVGUBMFMLF-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (R)-3-ethoxy-4-(1,2,2-trimethyl-propylamino)-cyclobut-3-ene-1,2-dione 在 oxone 、 sodium ethanolate 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-[[(2R)-3,3-dimethylbutan-2-yl]amino]-4-[[2-(pyridin-3-ylamino)pyrimidin-4-yl]amino]cyclobut-3-ene-1,2-dione
  参考文献：
  名称：

  Hit to Lead optimization of a novel class of squarate-containing polo-like kinases inhibitors

  摘要：

  A high throughput screening (HTS) hit, 1 (Plk1 K-i = 2.2 mu M) was optimized and evaluated for the enzymatic inhibition of Plk-1 kinase. Molecular modeling suggested the importance of adding a hydrophobic aromatic amine side chain in order to improve the potency by a classic kinase H-donor-acceptor binding mode. Extensive SAR studies led to the discovery of 49 (Plk1 K-i = 5 nM; EC50 = 1.05 mu M), which demonstrated moderate efficacy at 100 mpk in a MiaPaCa tumor model, with no overt toxicity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.009

文献信息

• Hit to Lead optimization of a novel class of squarate-containing polo-like kinases inhibitors
  作者：Qingwei Zhang、Zhiren Xia、Michael J. Mitten、Loren M. Lasko、Vered Klinghofer、Jennifer Bouska、Eric F. Johnson、Thomas D. Penning、Yan Luo、Vincent L. Giranda、Alexander R. Shoemaker、Kent D. Stewart、Stevan W. Djuric、Anil Vasudevan

  DOI：10.1016/j.bmcl.2012.10.009

  日期：2012.12

  A high throughput screening (HTS) hit, 1 (Plk1 K-i = 2.2 mu M) was optimized and evaluated for the enzymatic inhibition of Plk-1 kinase. Molecular modeling suggested the importance of adding a hydrophobic aromatic amine side chain in order to improve the potency by a classic kinase H-donor-acceptor binding mode. Extensive SAR studies led to the discovery of 49 (Plk1 K-i = 5 nM; EC50 = 1.05 mu M), which demonstrated moderate efficacy at 100 mpk in a MiaPaCa tumor model, with no overt toxicity. (C) 2012 Elsevier Ltd. All rights reserved.