6-(1H-benzo[d]imidazol-1-yl)pyrimidin-4-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 6-(1H-benzo[d]imidazol-1-yl)pyrimidin-4-amine
• 英文别名: 6-(Benzimidazol-1-yl)pyrimidin-4-amine；6-(benzimidazol-1-yl)pyrimidin-4-amine
• 化学式: C₁₁H₉N₅
• 分子量: 211.226
• InChiKey: CZCLLXSFDHMCEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  异硫氰酸乙酯 、 6-(1H-benzo[d]imidazol-1-yl)pyrimidin-4-amine 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 0.5h， 以46%的产率得到1-(6-(1H-benzo[d]imidazol-1-yl)pyrimidin-4-yl)-3-ethylthiourea
  参考文献：
  名称：

  Development of Multifunctional Pyrimidinylthiourea Derivatives as Potential Anti-Alzheimer Agents

  摘要：

  Starting from a screening-hit compound, via structure modifications and optimizations, a series of nonfused and nonassembly pyrimidinylthiourea derivatives (2-5) was designed, synthesized, and evaluated as novel multifunctional agents against Alzheimer's disease. Biological activity results demonstrated that compounds 5r and 5t exhibited potent inhibition and excellent selectivity toward acetylcholinesterase (AChE, Sr, IC50 = 0.204 mu M, SI > 196; St, IC50 = 0.067 mu M, SI > 597), specific metal-chelating ability, significant antioxidant effects, modulation of metal-induced A beta aggregation, inhibition of ROS production by copper redox cycle, low cytotoxicity, and moderate neuroprotection to human neuroblastoma SH-SY5Y cells. Moreover, compound Sr displayed appropriate blood brain barrier (BBB) permeability both in vitro and in vivo and could improve memory and cognitive function of, scopolamine-induced amnesia mice. The multifunctional profiles of Sr and its effectivity in AD mice highlight these structurally distinct pyrimidinylthiourea derivatives as prospective prototypes in the research of innovative multifunctional drugs for Alzheimer's disease.

  DOI：

  10.1021/acs.jmedchem.6b00636
• 作为产物：
  描述：

  苯并咪唑 、 4-氨基-6-氯嘧啶 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 21.0h， 以78%的产率得到6-(1H-benzo[d]imidazol-1-yl)pyrimidin-4-amine
  参考文献：
  名称：

  发现 4,6-二取代嘧啶作为热休克因子 1 (HSF1) 应激途径和 CDK9 的有效抑制剂†‡

  摘要：

  热休克因子 1 (HSF1) 是一种转录因子，在癌症中发挥关键作用，包括提供细胞在蛋白毒性应激下生存的机制。因此，抑制 HSF1 应激途径代表了癌症治疗中令人兴奋的新机会。我们采用公正的表型筛选来发现 HSF1 应激途径的抑制剂。使用这种方法，我们基于 4,6-嘧啶支架 (2.00 μM)确定了初始命中 ( 1 )。细胞 SAR 的优化使得抑制剂在 HSF1 表型测定中具有更高的效力（25、15 nM）。4,6-嘧啶25也被证明对 CDK9 酶具有高效能 (3 nM)。

  DOI：

  10.1039/c6md00159a

文献信息

• 取代嘧啶脲类化合物及其用途
  申请人：华东理工大学

  公开号：CN105418592B

  公开（公告）日：2018-02-16

  本发明涉及一种取代嘧啶脲类化合物及其用途。所述取代嘧啶脲类化合物为式I所示化合物(具体结构请见说明书或权利要求书)、或其立体异构体或药学上可接受的盐。体外活性测试表明：本发明公开的取代嘧啶脲类化合物具有胆碱酯酶抑制活性、螯合金属离子、抑制金属离子诱导的自由基产生和抑制金属离子诱导的Aβ聚集等性能。因此，本发明提供的取代嘧啶脲类化合物有望被用于制备治疗和/或预防阿尔茨海默病药物。
• Development of Multifunctional Pyrimidinylthiourea Derivatives as Potential Anti-Alzheimer Agents
  作者：Xiaokang Li、Huan Wang、Zhengyu Lu、Xinyu Zheng、Wei Ni、Jin Zhu、Yan Fu、Fulin Lian、Naixia Zhang、Jian Li、Haiyan Zhang、Fei Mao

  DOI：10.1021/acs.jmedchem.6b00636

  日期：2016.9.22

  Starting from a screening-hit compound, via structure modifications and optimizations, a series of nonfused and nonassembly pyrimidinylthiourea derivatives (2-5) was designed, synthesized, and evaluated as novel multifunctional agents against Alzheimer's disease. Biological activity results demonstrated that compounds 5r and 5t exhibited potent inhibition and excellent selectivity toward acetylcholinesterase (AChE, Sr, IC50 = 0.204 mu M, SI > 196; St, IC50 = 0.067 mu M, SI > 597), specific metal-chelating ability, significant antioxidant effects, modulation of metal-induced A beta aggregation, inhibition of ROS production by copper redox cycle, low cytotoxicity, and moderate neuroprotection to human neuroblastoma SH-SY5Y cells. Moreover, compound Sr displayed appropriate blood brain barrier (BBB) permeability both in vitro and in vivo and could improve memory and cognitive function of, scopolamine-induced amnesia mice. The multifunctional profiles of Sr and its effectivity in AD mice highlight these structurally distinct pyrimidinylthiourea derivatives as prospective prototypes in the research of innovative multifunctional drugs for Alzheimer's disease.
• Discovery of 4,6-disubstituted pyrimidines as potent inhibitors of the heat shock factor 1 (HSF1) stress pathway and CDK9
  作者：Carl S. Rye、Nicola E. A. Chessum、Scott Lamont、Kurt G. Pike、Paul Faulder、Julie Demeritt、Paul Kemmitt、Julie Tucker、Lorenzo Zani、Matthew D. Cheeseman、Rosie Isaac、Louise Goodwin、Joanna Boros、Florence Raynaud、Angela Hayes、Alan T. Henley、Emmanuel de Billy、Christopher J. Lynch、Swee Y. Sharp、Robert te Poele、Lisa O’ Fee、Kevin M. Foote、Stephen Green、Paul Workman、Keith Jones

  DOI：10.1039/c6md00159a

  日期：——

  Heat shock factor 1 (HSF1) is a transcription factor that plays key roles in cancer, including providing a mechanism for cell survival under proteotoxic stress. Therefore, inhibition of the HSF1-stress pathway represents an exciting new opportunity in cancer treatment. We employed an unbiased phenotypic screen to discover inhibitors of the HSF1-stress pathway. Using this approach we identified an initial

  热休克因子 1 (HSF1) 是一种转录因子，在癌症中发挥关键作用，包括提供细胞在蛋白毒性应激下生存的机制。因此，抑制 HSF1 应激途径代表了癌症治疗中令人兴奋的新机会。我们采用公正的表型筛选来发现 HSF1 应激途径的抑制剂。使用这种方法，我们基于 4,6-嘧啶支架 (2.00 μM)确定了初始命中 ( 1 )。细胞 SAR 的优化使得抑制剂在 HSF1 表型测定中具有更高的效力（25、15 nM）。4,6-嘧啶25也被证明对 CDK9 酶具有高效能 (3 nM)。