9-[(2-甲基苯甲基)氨基]-1,2,3,4-四氢吖啶-1-醇 | 104628-23-1

• 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
• 中文名称: 9-[(2-甲基苯甲基)氨基]-1,2,3,4-四氢吖啶-1-醇
• 英文名称: 9-(2-Methylbenzylamino)-1,2,3,4-tetrahydroacridin-1-ol
• 英文别名: 1,2,3,4-Tetrahydro-9-(((2-methylphenyl)methyl)amino)-1-acridinol；9-[(2-methylphenyl)methylamino]-1,2,3,4-tetrahydroacridin-1-ol
• CAS: 104628-23-1
• 化学式: C₂₁H₂₂N₂O
• 分子量: 318.418
• InChiKey: ASZXFMFROJTYBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  45.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  9-氨基-3,4-二氢吖啶-1(2H)-酮 在 四丁基硫酸氢铵 sodium hydroxide 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 为溶剂， 反应 6.0h， 生成 9-[(2-甲基苯甲基)氨基]-1,2,3,4-四氢吖啶-1-醇
  参考文献：
  名称：

  9-Amino-1,2,3,4-tetrahydroacridin-1-ols. Synthesis and evaluation as potential Alzheimer's disease therapeutics

  摘要：

  The synthesis of a series of 9-amino-1,2,3,4-tetrahydroacridin-1-ols is reported. These compounds are related to 1,2,3,4-tetrahydro-9-acridinamine (THA, tacrine). They inhibit acetylcholinesterase in vitro and are active in a model that may be predictive of activity in Alzheimer's disease--the scopolamine-induced impairment of 24-h memory of a passive dark-avoidance paradigm in mice. Two compounds, (+/-)-9-amino-1,2,3,4-tetrahydroacridin-1-ol maleate (1a, HP-029) and (+/-)-9-(benzylamino)-1,2,3,4-tetrahydroacridin-1-ol maleate (1p, HP-128), were also active in reversing the deficit in 72-h retention of a one-trial dark-avoidance task in rats, induced by ibotenic acid lesions in the nucleus basalis magnocellularis. In addition, compound 1 p showed potent in vitro inhibition of the uptake of radiolabeled noradrenaline and dopamine (IC50 = 0.070 and 0.30 microM, respectively). Compounds 1a and 1p, which showed less acute toxicity in both rats and mice than THA, are in phase II and phase I clinical trials, respectively, for Alzheimer's disease.

  DOI：

  10.1021/jm00128a024

文献信息

• 9-amino-1,2,3,4-tetrahydroacridin-1-ol and related compounds
  申请人：Hoechst-Roussel Pharmaceuticals Inc.

  公开号：US04695573A1

  公开（公告）日：1987-09-22

  There are disclosed compounds having the formula ##STR1## wherein n is 1, 2 or 3; X is hydrogen, loweralkyl, loweralkoxy, halogen, hydroxy, nitro, trifluoromethyl, NHCOR.sub.2 where R.sub.2 is loweralkyl, or NR.sub.3 R.sub.4 where R.sub.3 and R.sub.4 are independently hydrogen or loweralkyl; R is hydrogen or loweralkyl; R.sub.1 is hydrogen, loweralkyl, diloweralkylaminoloweralkyl, arylloweralkyl, diarylloweralkyl, furylloweralkyl, thienylloweralkyl, oxygen-bridged arylloweralkyl, oxygen-bridged diarylloweralkyl, oxygen-bridged furylloweralkyl or oxygen-bridged thienylloweralkyl; Y is C.dbd.O or CR.sub.5 OH where R.sub.5 is hydrogen or loweralkyl; Z is CH.sub.2 or C.dbd.CR.sub.6 R.sub.7 where R.sub.6 and R.sub.7 are independently hydrogen or loweralkyl; or Y and Z taken together is CR.sub.5 .dbd.CH where CR.sub.5 and CH correspond to Y and Z respectively; an optical antipode thereof, or a pharmaceutically acceptable acid addition salt thereof, which are useful for enhancing memory, methods for synthesizing them, and pharmaceutical compositions comprising an effective memory enhancing amount of such a compound.

  披露了具有以下结构式的化合物##STR1##其中n为1、2或3；X为氢、较低烷基、较低烷氧基、卤素、羟基、硝基、三氟甲基、NHCOR.sub.2，其中R.sub.2为较低烷基，或NR.sub.3 R.sub.4，其中R.sub.3和R.sub.4独立地为氢或较低烷基；R为氢或较低烷基；R.sub.1为氢、较低烷基、二较低烷基氨基较低烷基、芳基较低烷基、二芳基较低烷基、呋喃基较低烷基、噻吩基较低烷基、氧桥芳基较低烷基、氧桥二芳基较低烷基、氧桥呋喃基较低烷基或氧桥噻吩基较低烷基；Y为C.dbd.O或CR.sub.5 OH，其中R.sub.5为氢或较低烷基；Z为CH.sub.2或C.dbd.CR.sub.6 R.sub.7，其中R.sub.6和R.sub.7独立地为氢或较低烷基；或Y和Z一起为CR.sub.5 .dbd.CH，其中CR.sub.5和CH分别对应于Y和Z；其光学对映体，或其药学上可接受的酸盐，用于增强记忆，合成它们的方法，以及包含有效增强记忆量的这种化合物的药物组合物。
• Method of preparing 9-amino-1,2,3,4,-tetrahydroacridin-1-ones and
  申请人：Hoechst-Roussel Pharmaceuticals, Inc.

  公开号：US04835275A1

  公开（公告）日：1989-05-30

  There are disclosed compounds having the formula ##STR1## wherein n is 1, 2 or 3; X is hydrogen, loweralkyl, loweralkoxy, halogen, hydroxy, nitro, trifluoromethyl, NHCOR.sub.2 where R.sub.2 is loweralkyl, or NR.sub.3 R.sub.4 where R.sub.3 and R.sub.4 are independently hydrogen or loweralkyl; R is hydrogen or loweralkyl; R.sub.1 is hydrogen, loweralkyl, diloweralkylaminoloweralkyl, arylloweralkyl, diarylloweralkyl, furylloweralkyl, thienylloweralkyl, oxygen-bridged arylloweralkyl, oxygen-bridged diarylloweralkyl, oxygen-bridged furylloweralkyl or oxygen-bridged thienylloweralkyl; Y is C.dbd.O or CR.sub.5 OH where R.sub.5 is hydrogen or loweralkyl; Z is CH.sub.2 or C.dbd.CR.sub.6 R.sub.7 where R.sub.6 and R.sub.7 are independently hydrogen or loweralkyl; or Y and Z taken together is CR.sub.5 .dbd.CH where CR.sub.5 and CH correspond to Y and Z respectively; an optical antipode thereof, or a pharmaceutically acceptable acid addition salt thereof, which are useful for enhancing memory, methods for synthesizing them, and pharmaceutical compositions comprising an effective memory enhancing amount of such a compound.

  公开了具有以下结构式的化合物##STR1##其中n为1、2或3；X为氢、低烷基、低烷氧基、卤素、羟基、硝基、三氟甲基、NHCOR.sub.2，其中R.sub.2为低烷基，或NR.sub.3R.sub.4，其中R.sub.3和R.sub.4独立地为氢或低烷基；R为氢或低烷基；R.sub.1为氢、低烷基、二低烷氨基低烷基、芳基低烷基、二芳基低烷基、呋喃基低烷基、噻吩基低烷基、氧桥芳基低烷基、氧桥二芳基低烷基、氧桥呋喃基低烷基或氧桥噻吩基低烷基；Y为C.dbd.O或CR.sub.5OH，其中R.sub.5为氢或低烷基；Z为CH.sub.2或C.dbd.CR.sub.6R.sub.7，其中R.sub.6和R.sub.7独立地为氢或低烷基；或Y和Z一起为CR.sub.5.dbd.CH，其中CR.sub.5和CH分别对应于Y和Z；其光学对映体或其药学上可接受的酸加盐，它们对增强记忆有用，方法用于合成它们，以及包含有效的增强记忆量的这种化合物的制药组合物。
• 9-Amino-3,4-dihydroacridines and related compounds useful for enhancing
  申请人：Hoechst-Roussel Pharmaceuticals, Inc.

  公开号：US04839364A1

  公开（公告）日：1989-06-13

  There are disclosed compounds having the formula ##STR1## wherein n is 1, 2 or 3; X is hydrogen, loweralkyl, loweralkoxy, halogen, hydroxy, nitro, trifluoromethyl, NHCOR.sub.2 where R.sub.2 is loweralkyl, or NR.sub.3 R.sub.4 where R.sub.3 and R.sub.4 are independently hydrogen or loweralkyl; R is hydrogen or loweralkyl; R.sub.1 is hydrogen, loweralkyl, diloweralkylaminoloweralkyl, arylloweralkyl, diarylloweralkyl, furylloweralkyl, thienylloweralkyl, oxygen-bridged arylloweralkyl, oxygen-bridged diarylloweralkyl, oxygen-bridged furylloweralkyl or oxygen-bridged thienylloweralkyl; Y is C.dbd.O or CR.sub.5 OH where R.sub.5 is hydrogen or loweralkyl; Z is CH.sub.2 or C.dbd.CR.sub.6 R.sub.7 where R.sub.6 and R.sub.7 are independently hydrogen or loweralkyl; or Y and Z taken together is CR.sub.5 .dbd.Ch where CR.sub.5 and CH correspond to Y and Z respectively; an optical antipode thereof, or a pharmaceutically acceptable acid addition salt thereof, which are useful for enhancing memory, methods for synthesizing them, and pharmaceutical compositions comprising an effective memory enhancing amount of such a compound.

  公开了具有以下式子的化合物：##STR1## 其中n为1，2或3；X为氢，低碳基，低碳氧基，卤素，羟基，硝基，三氟甲基，NHCOR.sub.2，其中R.sub.2为低碳基，或NR.sub.3 R.sub.4，其中R.sub.3和R.sub.4分别为氢或低碳基；R为氢或低碳基；R.sub.1为氢，低碳基，二低碳基氨基低碳基，芳基低碳基，二芳基低碳基，呋喃基低碳基，噻吩基低碳基，氧桥联芳基低碳基，氧桥联二芳基低碳基，氧桥联呋喃基低碳基或氧桥联噻吩基低碳基；Y为C.dbd.O或CR.sub.5 OH，其中R.sub.5为氢或低碳基；Z为CH.sub.2或C.dbd.CR.sub.6 R.sub.7，其中R.sub.6和R.sub.7独立地为氢或低碳基；或Y和Z一起为CR.sub.5.dbd.Ch，其中CR.sub.5和CH分别对应于Y和Z；其光学异构体，或其药学上可接受的酸加盐，其可用于增强记忆的方法，用于合成它们的方法，以及包含有效的增强记忆量的这种化合物的制药组合物。
• 9-Amino-1,2,3,4-tetrahydroacridin-1-ol and related compounds, a process for their preparation and their use as medicaments
  申请人：HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED

  公开号：EP0179383B1

  公开（公告）日：1991-05-29
• SHUTSKE, GREGORY M.;PIERRAT, FRANK A.
  作者：SHUTSKE, GREGORY M.、PIERRAT, FRANK A.

  DOI：——

  日期：——