9-(thiophen-2-ylmethylamino)-3,4-dihydro-2H-acridin-1-one | 104628-12-8

• 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: 9-(thiophen-2-ylmethylamino)-3,4-dihydro-2H-acridin-1-one
• CAS: 104628-12-8
• 化学式: C₁₈H₁₆N₂OS
• 分子量: 308.404
• InChiKey: OANFKRNIOKICTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  70.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  9-(thiophen-2-ylmethylamino)-3,4-dihydro-2H-acridin-1-one 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 2.0h， 以47%的产率得到(2E)-but-2-enedioic acid; 9-[(thiophen-2-ylmethyl)amino]-1,2,3,4-tetrahydroacridin-1-ol
  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
• 作为产物：
  描述：

  2-[(3-氧代-1-环己烯-1-基)氨基]苯甲腈 在 四丁基硫酸氢铵 、 copper(l) chloride sodium hydroxide 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 9.0h， 生成 9-(thiophen-2-ylmethylamino)-3,4-dihydro-2H-acridin-1-one
  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, 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：——
• SHUTSKA, GREGORY M.;PIERRAT, FRANK A.
  作者：SHUTSKA, GREGORY M.、PIERRAT, FRANK A.

  DOI：——

  日期：——
• SHUTSKE, GREGORY M.;PIERRAT, FRANK A.;KAPPLES, KEVIN J.;CORNFELDT, MICHAE+, J. MED. CHEM., 32,(1989) N, C. 1805-1813
  作者：SHUTSKE, GREGORY M.、PIERRAT, FRANK A.、KAPPLES, KEVIN J.、CORNFELDT, MICHAE+

  DOI：——

  日期：——
• EP2681554B1
  申请人：——

  公开号：EP2681554B1

  公开（公告）日：2017-08-09