4-fluoro-N-[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]-benzamide hydrochloride | 1314741-38-2

• 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
• 英文名称: 4-fluoro-N-[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]-benzamide hydrochloride
• 英文别名: C6-3KW/HCl；4-fluoro-N-[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]benzamide;hydrochloride
• CAS: 1314741-38-2
• 化学式: C₂₃H₂₄FN₃O*ClH
• 分子量: 413.922
• InChiKey: PAINQULSLLEVJB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.91
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  54
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  9-氯-1,2,3,4-四氢吖啶 在 N-甲基吗啉 、 盐酸 、 2-chloro-4,6-dimethyl-1,3,5-triazine 、 sodium iodide 、 苯酚 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 16.03h， 生成 4-fluoro-N-[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]-benzamide hydrochloride
  参考文献：
  名称：

  Synthesis, biological activity and HPLC validation of 1,2,3,4-tetrahydroacridine derivatives as acetylcholinesterase inhibitors

  摘要：

  The synthesis and biochemical evaluation of new hybrids of tacrine (THA) and 4-fluorobenzoic acid (4-FBA) possessing activity towards acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition are presented. The compounds of interest were obtained from the reaction of activated 4-FBA and diamino derivatives of 1,2,3,4-tetrahydroacridine. The compounds C6-2KW/HCl, C6-4KW/HCl and C6-3KW/HCl have four-fold higher antiacetylcholinesterase activity than THA. All of the acquired compounds present higher selectivity towards AChE than THA and lower selectivity towards BuChE. In addition, a rapid, selective and stability-indicating HPLC method was developed and validated for the determination of C6-2KW/HCl, C6-3KW/HCl and C6-4KW/HCl. THA and 4-FBA were found to be the main impurities. Chromatographic separation was achieved isocratically on a Waters Symmetry C18 150 x 3.9 mm, 4 mu m column with a mobile phase of acetonitrile/buffer (17 mM sodium dodecyl sulphate and 83 mM sodium dihydrogen phosphate, 50:50 v/v) (overall pH 4). A 1.5 ml/min flow rate and a 247 nm wavelength were chosen for this method. C6-2KW/HCl, C6-3KW/HCl and C6-4KW/HCl were subjected to acidic and basic hydrolysis, chemical oxidation, thermal exposition at 60 degrees C and intense UV light. The limits of detection (LOD) and quantification (LOQ) were less than 2 mu g/ml and 6 mu g/ml for C6-2KW/HCl, C6-3KW/HCl and C6-4KW/HCl, 0.04 mu g/ml and 0.12 mu g/ml for THA, 0.42 mu g/ml and 1.41 mu g/ml for 4-FBA, respectively. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.04.038

文献信息

• Synthesis, biological activity and HPLC validation of 1,2,3,4-tetrahydroacridine derivatives as acetylcholinesterase inhibitors
  作者：Paweł Szymanski、Adam Karpiński、Elzbieta Mikiciuk-Olasik

  DOI：10.1016/j.ejmech.2011.04.038

  日期：2011.8

  The synthesis and biochemical evaluation of new hybrids of tacrine (THA) and 4-fluorobenzoic acid (4-FBA) possessing activity towards acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition are presented. The compounds of interest were obtained from the reaction of activated 4-FBA and diamino derivatives of 1,2,3,4-tetrahydroacridine. The compounds C6-2KW/HCl, C6-4KW/HCl and C6-3KW/HCl have four-fold higher antiacetylcholinesterase activity than THA. All of the acquired compounds present higher selectivity towards AChE than THA and lower selectivity towards BuChE. In addition, a rapid, selective and stability-indicating HPLC method was developed and validated for the determination of C6-2KW/HCl, C6-3KW/HCl and C6-4KW/HCl. THA and 4-FBA were found to be the main impurities. Chromatographic separation was achieved isocratically on a Waters Symmetry C18 150 x 3.9 mm, 4 mu m column with a mobile phase of acetonitrile/buffer (17 mM sodium dodecyl sulphate and 83 mM sodium dihydrogen phosphate, 50:50 v/v) (overall pH 4). A 1.5 ml/min flow rate and a 247 nm wavelength were chosen for this method. C6-2KW/HCl, C6-3KW/HCl and C6-4KW/HCl were subjected to acidic and basic hydrolysis, chemical oxidation, thermal exposition at 60 degrees C and intense UV light. The limits of detection (LOD) and quantification (LOQ) were less than 2 mu g/ml and 6 mu g/ml for C6-2KW/HCl, C6-3KW/HCl and C6-4KW/HCl, 0.04 mu g/ml and 0.12 mu g/ml for THA, 0.42 mu g/ml and 1.41 mu g/ml for 4-FBA, respectively. (C) 2011 Elsevier Masson SAS. All rights reserved.