| 1214274-46-0

• 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: 1214274-46-0
• 化学式: C₂₂H₃₀BrN₃O
• 分子量: 432.404
• InChiKey: DLUXPPBMHHROLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.99
• 重原子数：
  27.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  54.02
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3-(4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazol-3-yloxy)propan-1-ol 、 在 potassium carbonate 、 potassium iodide 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以46%的产率得到5-(3-{[4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazol-3-yl]oxy}propoxy)-N-[4-(1,2,3,4-tetrahydroacridin-9-ylamino)butyl]pentanamide
  参考文献：
  名称：

  Hybrid Molecules from Xanomeline and Tacrine: Enhanced Tacrine Actions on Cholinesterases and Muscarinic M₁ Receptors

  摘要：

  A set of amide- and amine-linked hybrid molecules comprising moieties of the orthosteric M-1 muscarinic receptor agonist xanomeline and the cholinesterase inhibitor and allosteric receptor modulator tacrine were prepared with varying spacer length of 10-17 atoms. The hybrids inhibited acetylcholinesterase with similar or higher potency compared to tacrine. M, receptor binding affinity was similar or higher relative to xanomeline and far higher relative to tacrine. Affinities hardly changed when the receptors' orthosteric site was Occupied by all inverse agonist ligand. When Occupied by the orthosteric activator acetylcholine, affinity for the hybrids declined to unmeasureably low levels. Hybrids did not activate M-1 receptors. In vivo studies assaying cognition impairment in rats induced by scopolamine revealed pronounced enhancement of scopolamine action. Taken together, instead of dualsteric (simultaneous allosteric/orthosteric) binding, the hybrids seem to prefer purely allosteric binding at the inactive M-1 receptor.

  DOI：

  10.1021/jm901616h
• 作为产物：
  描述：

  5-溴戊酰氯 、 9-(4-aminobutylamino)-1,2,3,4-tetrahydroacridine 以 二氯甲烷 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  Hybrid Molecules from Xanomeline and Tacrine: Enhanced Tacrine Actions on Cholinesterases and Muscarinic M₁ Receptors

  摘要：

  A set of amide- and amine-linked hybrid molecules comprising moieties of the orthosteric M-1 muscarinic receptor agonist xanomeline and the cholinesterase inhibitor and allosteric receptor modulator tacrine were prepared with varying spacer length of 10-17 atoms. The hybrids inhibited acetylcholinesterase with similar or higher potency compared to tacrine. M, receptor binding affinity was similar or higher relative to xanomeline and far higher relative to tacrine. Affinities hardly changed when the receptors' orthosteric site was Occupied by all inverse agonist ligand. When Occupied by the orthosteric activator acetylcholine, affinity for the hybrids declined to unmeasureably low levels. Hybrids did not activate M-1 receptors. In vivo studies assaying cognition impairment in rats induced by scopolamine revealed pronounced enhancement of scopolamine action. Taken together, instead of dualsteric (simultaneous allosteric/orthosteric) binding, the hybrids seem to prefer purely allosteric binding at the inactive M-1 receptor.

  DOI：

  10.1021/jm901616h