2-((2-(1-benzylpiperidin-4-yl)ethyl)amino)-6-chloro-4-phenylpyridine-3,5-dicarbonitrile | 1456626-34-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-((2-(1-benzylpiperidin-4-yl)ethyl)amino)-6-chloro-4-phenylpyridine-3,5-dicarbonitrile
• 英文别名: 2-[2-(1-Benzylpiperidin-4-yl)ethylamino]-6-chloro-4-phenylpyridine-3,5-dicarbonitrile；2-[2-(1-benzylpiperidin-4-yl)ethylamino]-6-chloro-4-phenylpyridine-3,5-dicarbonitrile
• CAS: 1456626-34-8
• 化学式: C₂₇H₂₆ClN₅
• 分子量: 455.99
• InChiKey: CBUMRMKTVSNLKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(2-氨基乙基)-1-苄基哌啶 、 啶菌腈 在 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 15.0h， 以65%的产率得到2-((2-(1-benzylpiperidin-4-yl)ethyl)amino)-6-chloro-4-phenylpyridine-3,5-dicarbonitrile
  参考文献：
  名称：

  Synthesis, pharmacological assessment, and molecular modeling of 6-chloro-pyridonepezils: New dual AChE inhibitors as potential drugs for the treatment of Alzheimer's disease

  摘要：

  6-Chloro-pyridonepezils are chloropyridine donepezil hybrids designed by combining the N-benzylpiperidine moiety present in donepezil with the 2-chloropyridine-3,5-dicarbonitrile heterocyclic ring system, both connected by an appropriate polymethylene linker. 6-Chloro-pyridonepezils 1-8 were prepared by reaction of 2,6-dichloro-4-phenylpyridine-3,5-dicarbonitrile (13) [or 2,6-dichloropyridine3,5-dicarbonitrile (14)1 with suitable 2-(1-benzylpiperidin-4-yDalkylamines (9-12). The biological evaluation showed that these new compounds are cholinesterase inhibitors, in the submicromolar range, one of them (6) being a potent hBuChE inhibitor (IC50 = 0.47 +/- 0.08 mu M). 6-Chloro-pyridonepezils 4, 7 and 8 are potent hAChE inhibitors showing IC50 in the 0.013-0.054 mu M range. Particularly, 6-chloro-pyridonepezil 8 is 625-fold more selective for hAChE than for hBuChE and compared to donepezil is equipotent for the inhibition of hAChE. Molecular modeling investigation on 6-chloro-pyridonepezils 4, 6-8 supports its dual AChE inhibitory profile, by binding simultaneously at the catalytic active and at peripheral anionic sites of the enzyme. The in vitro Blood Brain Barrier (BBB) and theoretical ADME analysis of 6-chloro-pyridonepezils 1-8 have been carried out. Overall, compound 8, is a permeable potent and selective dual AChEI that can be considered as a good candidate with potential impact for further pharmacological development in Alzheimer's therapy. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.06.021