N-benzyl-2-[4-(4-chlorobenzyl)piperazin-1-yl]pyrimidin-4-amine | 1296135-54-0

• 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: N-benzyl-2-[4-(4-chlorobenzyl)piperazin-1-yl]pyrimidin-4-amine
• 英文别名: N-benzyl-2-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]pyrimidin-4-amine
• CAS: 1296135-54-0
• 化学式: C₂₂H₂₄ClN₅
• 分子量: 393.919
• InChiKey: KVNDUVHFPYTHQS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  44.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  苄胺 在 N,N-二异丙基乙胺 作用下， 以 乙醇 、 正丁醇 为溶剂， 反应 3.08h， 生成 N-benzyl-2-[4-(4-chlorobenzyl)piperazin-1-yl]pyrimidin-4-amine
  参考文献：
  名称：

  Design, synthesis and structure–activity relationship (SAR) studies of 2,4-disubstituted pyrimidine derivatives: Dual activity as cholinesterase and Aβ-aggregation inhibitors

  摘要：

  A novel class of 2,4-disubstituted pyrimidines (7a-u, 8a-f, 9a-e) that possess substituents with varying steric and electronic properties at the C-2 and C-4 positions, were designed, synthesized and evaluated as dual cholinesterase and amyloid-beta (A beta)-aggregation inhibitors. In vitro screening identified N-(naphth-1-ylmethyl)-2-(pyrrolidin-1-yl)pyrimidin-4-amine (9a) as the most potent AChE inhibitor (IC50 = 5.5 mu M). Among this class of compounds, 2-(4-methylpiperidin-1-yl)-N-(naphth-1-ylmethyl) pyrimidin-4-amine (9e) was identified as the most potent and selective BuChE inhibitor (IC50 = 2.2 mu M, selectivity index = 11.7) and was about 5.7-fold more potent compared to the commercial, approved reference drug galanthamine (BuChE IC50 = 12.6 mu M). In addition, the selective AChE inhibitor N-benzyl-2-(4-methylpiperazin-1-yl)pyrimidin-4-amine (7d), exhibited good inhibition of hAChE-induced aggregation of A beta(1-40) fibrils (59% inhibition). Furthermore, molecular modeling studies indicate that a central pyrimidine ring serves as a suitable template to develop dual inhibitors of cholinesterase and AChE-induced A beta aggregation thereby targeting multiple pathological routes in AD. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.030

文献信息

• Design, synthesis and structure–activity relationship (SAR) studies of 2,4-disubstituted pyrimidine derivatives: Dual activity as cholinesterase and Aβ-aggregation inhibitors
  作者：Tarek Mohamed、Xiaobei Zhao、Lila K. Habib、Jerry Yang、Praveen P.N. Rao

  DOI：10.1016/j.bmc.2011.02.030

  日期：2011.4

  A novel class of 2,4-disubstituted pyrimidines (7a-u, 8a-f, 9a-e) that possess substituents with varying steric and electronic properties at the C-2 and C-4 positions, were designed, synthesized and evaluated as dual cholinesterase and amyloid-beta (A beta)-aggregation inhibitors. In vitro screening identified N-(naphth-1-ylmethyl)-2-(pyrrolidin-1-yl)pyrimidin-4-amine (9a) as the most potent AChE inhibitor (IC50 = 5.5 mu M). Among this class of compounds, 2-(4-methylpiperidin-1-yl)-N-(naphth-1-ylmethyl) pyrimidin-4-amine (9e) was identified as the most potent and selective BuChE inhibitor (IC50 = 2.2 mu M, selectivity index = 11.7) and was about 5.7-fold more potent compared to the commercial, approved reference drug galanthamine (BuChE IC50 = 12.6 mu M). In addition, the selective AChE inhibitor N-benzyl-2-(4-methylpiperazin-1-yl)pyrimidin-4-amine (7d), exhibited good inhibition of hAChE-induced aggregation of A beta(1-40) fibrils (59% inhibition). Furthermore, molecular modeling studies indicate that a central pyrimidine ring serves as a suitable template to develop dual inhibitors of cholinesterase and AChE-induced A beta aggregation thereby targeting multiple pathological routes in AD. (C) 2011 Elsevier Ltd. All rights reserved.