2-(3-(4-(3-(tert-butylamino)-7-methylimidazo[1,2-a]pyridin-2-yl)phenoxy)propyl)isoindoline-1,3-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(3-(4-(3-(tert-butylamino)-7-methylimidazo[1,2-a]pyridin-2-yl)phenoxy)propyl)isoindoline-1,3-dione
• 英文别名: 2-[3-[4-[3-(Tert-butylamino)-7-methylimidazo[1,2-a]pyridin-2-yl]phenoxy]propyl]isoindole-1,3-dione；2-[3-[4-[3-(tert-butylamino)-7-methylimidazo[1,2-a]pyridin-2-yl]phenoxy]propyl]isoindole-1,3-dione
• 化学式: C₂₉H₃₀N₄O₃
• 分子量: 482.582
• InChiKey: BBTGVNUNXWXFLO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  75.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-(3-溴丙基)苯二胺 在 potassium carbonate 、 氯化铵 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 8.0h， 生成 2-(3-(4-(3-(tert-butylamino)-7-methylimidazo[1,2-a]pyridin-2-yl)phenoxy)propyl)isoindoline-1,3-dione
  参考文献：
  名称：

  Discovery of imidazopyridines containing isoindoline-1,3-dione framework as a new class of BACE1 inhibitors: Design, synthesis and SAR analysis

  摘要：

  Alzheimer's disease is characterized by chronic neurodegeneration leading to dementia. The main cause of neurodegeneration is considered to be the accumulation of amyloid-beta. Inhibiting BACE1 is a well studied approach to lower the burden of amyloid-beta aggregates. We designed a series of imidazopyridines-based compounds bearing phthalimide moieties as inhibitors of BACE1. The compounds 8a-o were synthesized by the Groebke Blackburn Bienayme three-component reaction of heteroaromatic amidines, aldehydes and isocyanides. Evaluating the BACE1 inhibitory effects of the synthesized compounds revealed that introducing an aminocyclohexyl moiety in the imidazopyridine core resulted in a significant improvement in its BACE1 inhibitory potential. In this regard, compound 8e was the most potent against BACE1 with an IC50 value of 2.84 (+/- 0.95) mu M. Molecular docking revealed that the nitrogen atom of imidazopyridines and the oxygen atom of the phenoxypropyl linker were involved in hydrogen bound interactions with Asp228 and Asp32 of BACE1 active site, respectively. The phthalimide moiety oriented toward the flap pocket and interacted with phe108, 11e110, Trp115, 11e118 through van der Waal's and hydrophobic interactions. These findings demonstrate that imidazopyridines-based compounds bearing phthalimide moiety have the potential to decrease amyloid-beta levels and ameliorate the symptoms of Alzheimer's disease. (C) 2017 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2017.06.040