2-chloro-N-(4-methylbenzyl)pyrimidin-4-amine | 945895-76-1

• 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: 2-chloro-N-(4-methylbenzyl)pyrimidin-4-amine
• 英文别名: 2-chloro-N-[(4-methylphenyl)methyl]pyrimidin-4-amine
• CAS: 945895-76-1
• 化学式: C₁₂H₁₂ClN₃
• mdl: MFCD09756914
• 分子量: 233.7
• InChiKey: ISLIIYMZSIFWKY-UHFFFAOYSA-N

物化性质

• 沸点：
  418.7±25.0 °C(Predicted)
• 密度：
  1.268±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-氨基-1-苄基哌啶 、 2-chloro-N-(4-methylbenzyl)pyrimidin-4-amine 在 N,N-二异丙基乙胺 作用下， 以 正丁醇 为溶剂， 以45%的产率得到N(2)-(1-benzylpiperidin-4-yl)-N(4)-(4-methylbenzyl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Development and evaluation of multifunctional agents for potential treatment of Alzheimer’s disease: Application to a pyrimidine-2,4-diamine template

  摘要：

  We investigated a group of 2-benzylpiperidin-N-benzylpyrimidin-4-amines with various electron-withdrawing or electron-donating groups (EWGs or EDGs, respectively) as multi-targeted Alzheimer's disease (AD) therapeutics. The synthesized derivatives were screened for anti-cholinesterase (AChE and BuChE), anti-A beta-aggregation (AChE- and self-induced) and anti-beta-secretase (BACE-1) activities in an effort to identify lead, multifunctional candidates as part of our multi-targeted approach to treat AD. Biological assessment revealed that the nature of the substituent on the C-4 benzylamine group (e.g., halogen vs methoxy-based) greatly affected the biological profile. In vitro screening identified N-2-(1-benzylpiperidin-4-yl)-N-4-(3,4-dimethoxybenzyl) pyrimidine-2,4-diamine (7h) as the lead candidate with a dual ChE (AChE IC50 = 9.9 mu M; BuChE IC50 = 11.4 mu M), A beta-aggregation (AChE-induced = 59.3%; self-induced = 17.4% at 100 mu M) and BACE-1 (34% inhibition at 10 mu M) inhibitory profile along with good cell viability (% neuroblastoma cell viability at 40 mu M = 81.0%). Molecular modeling studies indicate that a central pyrimidine-2,4-diamine ring serves as a suitable template to develop novel small molecule candidates to target multiple pathological routes in AD. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.077
• 作为产物：
  描述：

  2,4-二氯嘧啶 、 4-甲基苄胺 在 N,N-二异丙基乙胺 作用下， 以 乙醇 为溶剂， 以73%的产率得到2-chloro-N-(4-methylbenzyl)pyrimidin-4-amine
  参考文献：
  名称：

  从头设计的方法针对包膜蛋白袋，以鉴定抗登革热病毒的小分子。

  摘要：

  登革热是一种由蚊子传播的病毒性疾病，已成为全球主要的公共卫生问题。该疾病具有广泛的临床表现，从轻度感冒样疾病到更严重的出血性登革热和登革热休克综合症。目前，尚无用于治疗该疾病的批准药物或有效疫苗。包膜蛋白（E）是病毒体表面的主要成分。该蛋白在病毒进入过程中起关键作用，构成了抗病毒药物开发的诱人靶标。E蛋白的晶体结构表明存在被洗涤剂正辛基-β-d-葡萄糖苷（β-OG）占据的疏水口袋。该口袋位于结构域I和II之间的铰链区，对于病毒体与宿主细胞融合所需的低pH触发构象重排很重要。针对与E结合并充当病毒进入抑制剂的新型分子的设计，我们通过从头开始在疏水位点（β-OG）内“生长”分子进行了从头设计方法。从产生的24万多个小分子中，选择2,4个嘧啶支架作为最佳候选物，从中一个合成的化合物显示出微摩尔活性。为此，对分子进行了基于分子动力学的优化，并通过计算机设计了三十种衍生物，对其进行了合成并对其抑制登

  DOI：

  10.1016/j.ejmech.2019.111628

文献信息

• Small-molecule pyrimidine inhibitors of the cdc2-like (Clk) and dual specificity tyrosine phosphorylation-regulated (Dyrk) kinases: Development of chemical probe ML315
  作者：Thomas C. Coombs、Cordelle Tanega、Min Shen、Jenna L. Wang、Douglas S. Auld、Samuel W. Gerritz、Frank J. Schoenen、Craig J. Thomas、Jeffrey Aubé

  DOI：10.1016/j.bmcl.2013.02.096

  日期：2013.6

  Substituted pyrimidine inhibitors of the Clk and Dyrk kinases have been developed, exploring structure-activity relationships around four different chemotypes. The most potent compounds have low-nanomolar inhibitory activity against Clk1, Clk2, Clk4, Dyrk1A and Dyrk1B. Kinome scans with 442 kinases using agents representing three of the chemotypes show these inhibitors to be highly selective for the Clk and Dyrk families. Further off-target pharmacological evaluation with ML315, the most selective agent, supports this conclusion. (C) 2013 Elsevier Ltd. All rights reserved.