(S)-ethyl 5-amino-4-(4-methoxyphenyl)-2-methyl-1,4,6,7,8,9-hexahydrobenzo[b][1,8]naphthyridine-3-carboxylate | 1347740-32-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (S)-ethyl 5-amino-4-(4-methoxyphenyl)-2-methyl-1,4,6,7,8,9-hexahydrobenzo[b][1,8]naphthyridine-3-carboxylate
• 英文别名: ethyl (4S)-5-amino-4-(4-methoxyphenyl)-2-methyl-1,4,6,7,8,9-hexahydrobenzo[b][1,8]naphthyridine-3-carboxylate
• CAS: 1347740-32-2
• 化学式: C₂₃H₂₇N₃O₃
• 分子量: 393.486
• InChiKey: ZNRGREFWBCWZAU-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  86.5
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (+/-)-p-Methoxytacripyrine 生成 (S)-ethyl 5-amino-4-(4-methoxyphenyl)-2-methyl-1,4,6,7,8,9-hexahydrobenzo[b][1,8]naphthyridine-3-carboxylate 、 (S)-ethyl 5-amino-4-(4-methoxyphenyl)-2-methyl-1,4,6,7,8,9-hexahydrobenzo[b][1,8]naphthyridine-3-carboxylate
  参考文献：
  名称：

  Tacripyrines, the First Tacrine−Dihydropyridine Hybrids, as Multitarget-Directed Ligands for the Treatment of Alzheimer’s Disease

  摘要：

  Tacripyrines (1-14) have been designed by combining an ACNE inhibitor (tacrine) with a calcium antagonist such as nimodipine and are targeted to develop a multitarget therapeutic strategy to confront AD. Tacripyrines are selective and potent ACNE inhibitors in the nanomolar range. The mixed type inhibition of hAChE activity of compound 11 (IC50 105 +/- 15 nM) is associated to a 30.7 +/- 8.6% inhibition of the proaggregating action of ACNE on the A beta and a moderate inhibition of A beta self-aggregation (34.9 +/- 5.4%). Molecular modeling indicates that binding of compound 11 to the ACNE PAS mainly involves the (R)-11 enantiomer, which also agrees with the noncompetitive inhibition mechanism exhibited by p-methoxytacripyrine 11. Tacripyrines are neuroprotective agents, show moderate Ca2+ channel blocking effect, and cross the blood-brain barrier, emerging as lead candidates for treating AD.

  DOI：

  10.1021/jm801292b

文献信息

• Chemical and Pharmacological Studies on Enantiomerically Pure p-Methoxytacripyrines, Promising Multi-Target-Directed Ligands for the Treatment of Alzheimer’s Disease
  作者：Manuela Bartolini、Marco Pistolozzi、Vincenza Andrisano、Javier Egea、Manuela G. López、Isabel Iriepa、Ignacio Moraleda、Enrique Gálvez、José Marco-Contelles、Abdelouahid Samadi

  DOI：10.1002/cmdc.201100239

  日期：2011.11.4

  The S and R isomers of p‐methoxytacripyrine, a recently developed multi‐target‐directed agent for the treatment of Alzheimer's disease, were investigated. The S enantiomer has emerged as a new promising drug candidate inhibiting cholinesterase activity, amyloid aggregation and showing significant neuroprotective properties against Aβ25–35‐induced cytotoxicity.

  该 小号 和 - [R 异构体的p -methoxytacripyrine，用于阿尔茨海默氏病的治疗中的最近开发的多目标定向剂，进行了调查。在小号的对映体已成为一个新的有希望的候选药物抑制胆碱酯酶活性，淀粉样蛋白聚集，并且显示抗Aβ显著神经保护特性25-35诱导的细胞毒性。