多奈哌齐杂质D | 844694-84-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 多奈哌齐杂质D
• 中文别名: 多奈哌齐杂质1
• 英文名称: deoxydonepezil
• 英文别名: 2-[(1-benzylpiperidin-4-yl)methyl]-5,6-dimethoxyindane；1-benzyl-4-[(5,6-dimethoxy-2,3-dihydro-1H-inden-2-yl)methyl]piperidine
• CAS: 844694-84-4
• 化学式: C₂₄H₃₁NO₂
• 分子量: 365.516
• InChiKey: DUOWFFYJKGBOQB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  多奈哌齐杂质D 在 盐酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 以161 mg的产率得到1-苄基-4-((5,6-二甲氧基-2,3-二氢-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
• 作为产物：
  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

文献信息

• Impurities of Donepezil
  申请人：Krizmanic Irena

  公开号：US20090298879A1

  公开（公告）日：2009-12-03

  The present invention relates to impurities of donepezil, or a pharmaceutically acceptable salt thereof, which may be produced during synthesis and storage of donepezil, or a pharmaceutically-acceptable salt thereof, and to methods of identifying such impurities. The invention also relates to the use of these impurities in analytical techniques and to product that contain certain low levels of these impurities in particular the following impurities are disclosed: formula (I) and formula (II).

  本发明涉及多奈哌齐的杂质或其药学上可接受的盐，在多奈哌齐或其药学上可接受的盐的合成和储存过程中可能产生，以及识别这些杂质的方法。本发明还涉及在分析技术中使用这些杂质以及包含特定低水平这些杂质的产品，特别是披露以下杂质：式（I）和式（II）。
• PERCUTANEOUS ABSORPTION PREPARATION CONTAINING RIVASTIGMINE
  申请人：Samyang Biopharmaceuticals Corporation

  公开号：EP2654739B1

  公开（公告）日：2020-07-22
• [EN] IMPURITIES OF DONEPEZIL<br/>[FR] IMPURETÉS DU DONÉPÉZIL
  申请人：PLIVA ISTRAZIVANJE I RAZVOJ D

  公开号：WO2007135408A1

  公开（公告）日：2007-11-29

  [EN] The present invention relates to impurities of donepezil, or a pharmaceutically acceptable salt thereof, which may be produced during synthesis and storage of donepezil, or a pharmaceutically-acceptable salt thereof, and to methods of identifying such impurities.The invention also relates to the use of these impurities in analytical techniques and to product that contain certain low levels of these impurities in particular the following impurities are disclosed: formula (I) and formula (II).
  [FR] La présente invention concerne des impuretés du donépézil ou de l'un de ses sels pharmaceutiquement acceptables, lesdites impuretés pouvant être produites pendant la synthèse et le stockage du donépézil ou de son sel pharmaceutiquement acceptable. L'invention concerne également des procédés permettant d'identifier de telles impuretés et l'utilisation desdites impuretés dans le cadre de techniques analytiques, ainsi que des produits contenant des teneurs faibles de ces impuretés, notamment les impuretés suivantes :