5-bromo-6-(piperazin-1-yl)pyrimidin-4-amine | 1445972-63-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5-bromo-6-(piperazin-1-yl)pyrimidin-4-amine
• 英文别名: 4-(4-amino5-bromo-pyrimidin-4-yl)-piperazine；5-Bromo-6-piperazin-1-ylpyrimidin-4-amine；5-bromo-6-piperazin-1-ylpyrimidin-4-amine
• CAS: 1445972-63-3
• 化学式: C₈H₁₂BrN₅
• 分子量: 258.121
• InChiKey: CYVOXWZIMZAVMC-UHFFFAOYSA-N

物化性质

• 沸点：
  455.5±45.0 °C(Predicted)
• 密度：
  1.586±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-bromo-6-(piperazin-1-yl)pyrimidin-4-amine 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (±)-2-amino-1-(4-(6-amino-5-bromopyrimidin-4-yl)piperazin-1-yl)-3-(4-chlorophenyl) propan-1-one
  参考文献：
  名称：

  Integrating docking scores, interaction profiles and molecular descriptors to improve the accuracy of molecular docking: Toward the discovery of novel Akt1 inhibitors

  摘要：

  A set of forty-seven Akt1 inhibitors was used for the development of molecular docking based QSAR model by using nonlinear regression. The integration of docking scores, key interaction profiles and molecular descriptors remarkably improved the accuracy of the QSAR models, providing reasonable statistical parameters (R-train(2) = 0.948, R-test(2) = 0.907 and Q(cv)(2) = 0.794). The established MD-SVR model based structural modification of new 4-amino-pyrimidine derivatives was further performed, and six compounds 56a,b and 60a-d with good prediction activities were synthesized and biologically evaluated. All of these compounds exhibited promising Akt1 inhibitory and antiproliferative activities, suggesting the reliability and good application value of the established MD-SVR model in the development of Akt1 inhibitors. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.01.019
• 作为产物：
  描述：

  1-Boc-4-(6-氨基嘧啶-4-基)哌嗪 在 N-溴代丁二酰亚胺(NBS) 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 5-bromo-6-(piperazin-1-yl)pyrimidin-4-amine
  参考文献：
  名称：

  Integrating docking scores, interaction profiles and molecular descriptors to improve the accuracy of molecular docking: Toward the discovery of novel Akt1 inhibitors

  摘要：

  A set of forty-seven Akt1 inhibitors was used for the development of molecular docking based QSAR model by using nonlinear regression. The integration of docking scores, key interaction profiles and molecular descriptors remarkably improved the accuracy of the QSAR models, providing reasonable statistical parameters (R-train(2) = 0.948, R-test(2) = 0.907 and Q(cv)(2) = 0.794). The established MD-SVR model based structural modification of new 4-amino-pyrimidine derivatives was further performed, and six compounds 56a,b and 60a-d with good prediction activities were synthesized and biologically evaluated. All of these compounds exhibited promising Akt1 inhibitory and antiproliferative activities, suggesting the reliability and good application value of the established MD-SVR model in the development of Akt1 inhibitors. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.01.019

文献信息

• Discovery of 4-aminopyrimidine analogs as highly potent dual P70S6K/Akt inhibitors
  作者：Yufang Xiao、Bayard R. Huck、Ruoxi Lan、Lizbeth DeSelm、Xiaoling Chen、Hui Qiu、Constantin Neagu、Theresa Johnson、Igor Mochalkin、Anna Gardberg、Xuliang Jiang、Hui Tian、Vikram Dutt、Dusica Santos、Jared Head、Jennifer Jackson、Sakeena Syed、Jing Lin、Erik Wilker、Jianguo Ma、Anderson Clark、Andreas Machl、Donald Bankston、Christopher C.V. Jones、Andreas Goutopoulos、Brian Sherer

  DOI：10.1016/j.bmcl.2021.128352

  日期：2021.10

  PI3K/Akt/mTOR kinase pathway is associated with human cancers. A dual p70S6K/Akt inhibitor is sufficient to inhibit strong tumor growth and to block negative impact of the compensatory Akt feedback loop activation. A scaffold docking strategy based on an existing quinazoline carboxamide series identified 4-aminopyrimidine analog 6, which showed a single-digit nanomolar and a micromolar potencies in p70S6K

  PI3K/Akt/mTOR 激酶通路的激活与人类癌症有关。双重 p70S6K/Akt 抑制剂足以抑制强烈的肿瘤生长并阻止补偿性 Akt 反馈回路激活的负面影响。基于现有喹唑啉甲酰胺系列的支架对接策略确定了 4-氨基嘧啶类似物6，其在 p70S6K 和 Akt 酶测定中显示出个位数的纳摩尔和微摩尔效力。SAR 优化提高了 Akt 酶和 p70S6K 细胞的效力，降低了 hERG 的敏感性，并最终发现了有希望的候选者37，它在 p70S6K 和 Akt 生化分析中都表现出个位数的纳摩尔值，以及 hERG 活性（IC 50 = 17.4 微米）。该药物在抑制小鼠乳腺癌肿瘤生长方面表现出剂量依赖性功效，并且在 200 mg/kg po 的剂量下长达 24 小时覆盖超过 90% 的 pS6 抑制。
• Integrating docking scores, interaction profiles and molecular descriptors to improve the accuracy of molecular docking: Toward the discovery of novel Akt1 inhibitors
  作者：Wenhu Zhan、Daqiang Li、Jinxin Che、Liangren Zhang、Bo Yang、Yongzhou Hu、Tao Liu、Xiaowu Dong

  DOI：10.1016/j.ejmech.2014.01.019

  日期：2014.3

  A set of forty-seven Akt1 inhibitors was used for the development of molecular docking based QSAR model by using nonlinear regression. The integration of docking scores, key interaction profiles and molecular descriptors remarkably improved the accuracy of the QSAR models, providing reasonable statistical parameters (R-train(2) = 0.948, R-test(2) = 0.907 and Q(cv)(2) = 0.794). The established MD-SVR model based structural modification of new 4-amino-pyrimidine derivatives was further performed, and six compounds 56a,b and 60a-d with good prediction activities were synthesized and biologically evaluated. All of these compounds exhibited promising Akt1 inhibitory and antiproliferative activities, suggesting the reliability and good application value of the established MD-SVR model in the development of Akt1 inhibitors. (C) 2014 Elsevier Masson SAS. All rights reserved.