| 1621694-42-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• CAS: 1621694-42-5
• 化学式: C₄₂H₄₅Cl₂N₅O₃
• 分子量: 738.757
• InChiKey: DILQAUDZSJMDII-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.34
• 重原子数：
  52.0
• 可旋转键数：
  9.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  96.45
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  ethyl 1-(tert-butoxycarbonyl)-5-(4-chlorophenyl)-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine-9-carboxylate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二甲基甲酰胺 、 potassium hydroxide 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 42.58h， 生成 N-{5-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]pentyl}-5-(4-chlorophenyl)-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine-9-carboxamide 、
  参考文献：
  名称：

  Tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrids as a new family of anti-Alzheimer agents targeting β-amyloid, tau, and cholinesterase pathologies

  摘要：

  Optimization of an essentially inactive 3,4-dihydro-2H-pyrano[3,2-c]quinoline carboxylic ester derivative as acetylcholinesterase (AChE) peripheral anionic site (PAS)-binding motif by double O -> NH bioisosteric replacement, combined with molecular hybridization with the AChE catalytic anionic site (CAS) inhibitor 6-chlorotacrine and molecular dynamics-driven optimization of the length of the linker has resulted in the development of the trimethylene-linked 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine -6-chlorotacrine hybrid 5a as a picomolar inhibitor of human AChE (hAChE). The tetra-, penta-, and octamethylene-linked homologues 5b-d have been also synthesized for comparison purposes, and found to retain the nanomolar hAChE inhibitory potency of the parent 6-chlorotacrine. Further biological profiling of hybrids 5a-d has shown that they are also potent inhibitors of human butyrylcholinesterase and moderately potent A beta 42 and tau anti-aggregating agents, with IC50 values in the submicromolar and low micromolar range, respectively. Also, in vitro studies using an artificial membrane model have predicted a good brain permeability for hybrids 5a-d, and hence, their ability to reach their targets in the central nervous system. The multitarget profile of the novel hybrids makes them promising leads for developing anti-Alzheimer drug candidates with more balanced biological activities. (c) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.07.021