2-chloro-N-(3,4-dimethoxybenzyl)pyrimidin-4-amine | 1272123-93-9

• 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-(3,4-dimethoxybenzyl)pyrimidin-4-amine
• 英文别名: 2-chloro-N-[(3,4-dimethoxyphenyl)methyl]pyrimidin-4-amine
• CAS: 1272123-93-9
• 化学式: C₁₃H₁₄ClN₃O₂
• mdl: MFCD17293055
• 分子量: 279.726
• InChiKey: UCVIAWVCNKTBCY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  56.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-氨基-1-苄基哌啶 、 2-chloro-N-(3,4-dimethoxybenzyl)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)-(3,4-dimethoxybenzyl)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 、 3,4-二甲氧基苄胺 在 N,N-二异丙基乙胺 作用下， 以 乙醇 为溶剂， 反应 4.08h， 以88%的产率得到2-chloro-N-(3,4-dimethoxybenzyl)pyrimidin-4-amine
  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

文献信息

• Development and evaluation of multifunctional agents for potential treatment of Alzheimer’s disease: Application to a pyrimidine-2,4-diamine template
  作者：Tarek Mohamed、Jacky C.K. Yeung、Maryam S. Vasefi、Michael A. Beazely、Praveen P.N. Rao

  DOI：10.1016/j.bmcl.2012.05.077

  日期：2012.7

  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.