4-[[2-[[(2R)-3,3-dimethylbutan-2-yl]amino]-3,4-dioxocyclobuten-1-yl]amino]-2-(3,4,5-trimethoxyanilino)pyrimidine-5-carbonitrile | 1415548-29-6

• 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: 4-[[2-[[(2R)-3,3-dimethylbutan-2-yl]amino]-3,4-dioxocyclobuten-1-yl]amino]-2-(3,4,5-trimethoxyanilino)pyrimidine-5-carbonitrile
• CAS: 1415548-29-6
• 化学式: C₂₄H₂₈N₆O₅
• 分子量: 480.524
• InChiKey: JFKYVVBOEQNVTQ-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  148
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  (R)-3,3-二甲基-2-丁胺 在 sodium ethanolate 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 生成 4-[[2-[[(2R)-3,3-dimethylbutan-2-yl]amino]-3,4-dioxocyclobuten-1-yl]amino]-2-(3,4,5-trimethoxyanilino)pyrimidine-5-carbonitrile
  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.