(R)-3-(3,3-dimethylbutan-2-ylamino)-4-(2-(methylsulfonyl)pyrimidin-4-ylamino)cyclobut-3-ene-1,2-dione | 1415548-31-0

• 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: (R)-3-(3,3-dimethylbutan-2-ylamino)-4-(2-(methylsulfonyl)pyrimidin-4-ylamino)cyclobut-3-ene-1,2-dione
• 英文别名: 3-[[(2R)-3,3-dimethylbutan-2-yl]amino]-4-[(2-methylsulfonylpyrimidin-4-yl)amino]cyclobut-3-ene-1,2-dione
• CAS: 1415548-31-0
• 化学式: C₁₅H₂₀N₄O₄S
• 分子量: 352.414
• InChiKey: GMTZJLOKUOSTGS-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (R)-3-(3,3-dimethylbutan-2-ylamino)-4-(2-(methylsulfonyl)pyrimidin-4-ylamino)cyclobut-3-ene-1,2-dione 、 对三氟甲氧基苯胺 在 对甲苯磺酸 作用下， 以 四氢呋喃 为溶剂， 生成 3-[(2-{[4-(trifluoromethoxy)phenyl]amino}pyrimidin-4-yl)amino]-4-{[(1R)-1,2,2-trimethylpropyl]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
• 作为产物：
  描述：

  (R)-3-(3,3-dimethylbutan-2-ylamino)-4-(2-(methylthio)pyrimidin-4-ylamino)cyclobut-3-ene-1,2-dione 在 oxone 作用下， 以 甲醇 、 水 为溶剂， 以1.5 g的产率得到(R)-3-(3,3-dimethylbutan-2-ylamino)-4-(2-(methylsulfonyl)pyrimidin-4-ylamino)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

• WO2007/140233
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.