4-[(2,3-二氢-5,6-二甲氧基-1H-茚-2-基)甲基]哌啶盐酸盐 | 1034439-43-4

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 中文名称: 4-[(2,3-二氢-5,6-二甲氧基-1H-茚-2-基)甲基]哌啶盐酸盐
• 中文别名: 多奈哌齐杂质2
• 英文名称: 5,6-dimethoxy-2-[(4-piperidinyl)methyl]indane hydrochloride
• 英文别名: 5,6-Dimethoxy-2-[(4-piperidyl)methyl]indane Hydrochloride；4-[(5,6-dimethoxy-2,3-dihydro-1H-inden-2-yl)methyl]piperidine;hydrochloride
• CAS: 1034439-43-4
• 化学式: C₁₇H₂₅NO₂*ClH
• 分子量: 311.852
• InChiKey: FFYMHPLMHJQXRY-UHFFFAOYSA-N

物化性质

• 熔点：
  >140°C (dec.)
• 溶解度：
  可溶于二氯甲烷、DMSO、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  3.23
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  30.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[(2,3-二氢-5,6-二甲氧基-1H-茚-2-基)甲基]哌啶盐酸盐 、 苯甲醛 在 sodium cyanoborohydride 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 反应 16.0h， 以53%的产率得到多奈哌齐杂质D
  参考文献：
  名称：

  Novel Donepezil-Based Inhibitors of Acetyl- and Butyrylcholinesterase and Acetylcholinesterase-Induced β-Amyloid Aggregation

  摘要：

  A novel series of donepezil-tacrine hybrids designed to simultaneously interact with the active, peripheral and midgorge binding sites of acetylcholinesterase (AChE) have been synthesized and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE), and AChE-induced A beta aggregation. These compounds consist of a unit of tacrine or 6-chlorotacrine, which occupies the same position as tacrine at the AChE active site, and the 5,6-dimethoxy-2-[(4-piperidinyl)methyl]-1-indanone moiety of donepezil (or the indane derivative thereof), whose position along the enzyme gorge and the peripheral site can be modulated by a suitable tether that connects tacrine and donepezil fragments. All of the new compounds are highly potent inhibitors of bovine and human AChE and BChE, exhibiting IC50 values in the subnanomolar or low nanomolar range in most cases. Moreover, six out of the eight hybrids of the series, particularly those bearing an indane moiety, exhibit a significant A beta antiaggregating activity, which makes them promising anti-Alzheimer drug candidates.

  DOI：

  10.1021/jm8001313
• 作为产物：
  描述：

  多奈哌齐杂质L 在 盐酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 以57 mg的产率得到4-[(2,3-二氢-5,6-二甲氧基-1H-茚-2-基)甲基]哌啶盐酸盐
  参考文献：
  名称：

  Novel Donepezil-Based Inhibitors of Acetyl- and Butyrylcholinesterase and Acetylcholinesterase-Induced β-Amyloid Aggregation

  摘要：

  A novel series of donepezil-tacrine hybrids designed to simultaneously interact with the active, peripheral and midgorge binding sites of acetylcholinesterase (AChE) have been synthesized and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE), and AChE-induced A beta aggregation. These compounds consist of a unit of tacrine or 6-chlorotacrine, which occupies the same position as tacrine at the AChE active site, and the 5,6-dimethoxy-2-[(4-piperidinyl)methyl]-1-indanone moiety of donepezil (or the indane derivative thereof), whose position along the enzyme gorge and the peripheral site can be modulated by a suitable tether that connects tacrine and donepezil fragments. All of the new compounds are highly potent inhibitors of bovine and human AChE and BChE, exhibiting IC50 values in the subnanomolar or low nanomolar range in most cases. Moreover, six out of the eight hybrids of the series, particularly those bearing an indane moiety, exhibit a significant A beta antiaggregating activity, which makes them promising anti-Alzheimer drug candidates.

  DOI：

  10.1021/jm8001313