(R)-donepezil

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (R)-donepezil
• 英文别名: L-donepezil；donepezil；1-Benzyl-4-[(5,6-dimethoxy-1-indanon-2-YL)methyl]piperidine；(2R)-2-[(1-benzylpiperidin-4-yl)methyl]-5,6-dimethoxy-2,3-dihydroinden-1-one
• 化学式: C₂₄H₂₉NO₃
• 分子量: 379.499
• InChiKey: ADEBPBSSDYVVLD-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-donepezil 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 0.5h， 以100%的产率得到L-donepezil hydrochloric acid
  参考文献：
  名称：

  一种光学纯多奈哌齐的制备工艺

  摘要：

  本发明公开了一种光学纯多奈哌齐的制备工艺。该工艺采用手性的酒石酸类化合物作为拆分剂对多奈哌齐外消旋体进行拆分，得到其非对映体盐，对该非对映体盐进行重结晶纯化，最后碱化提取到光学纯的左旋多奈哌齐或右旋多奈哌齐。本发明所述的光学纯多奈哌齐的制备工艺操作简单可行、所需试剂便宜，拆分剂易得无毒且易于回收利用，适宜工业生产。

  公开号：

  CN103497145B
• 作为产物：
  描述：

  多萘哌齐碱 在 Beckman P/ACE MDQ Capillary Electrophoresis System equipped fused-silica capillaries (Polymicro Technologies, Phoenix, Arizona) of 50-μm ID cut with sulfobutyl ether β-cyclodextrin as chiral selector 作用下， 以 aq. buffer 为溶剂， 生成 (R)-donepezil 、 (S)-donepezil
  参考文献：
  名称：

  通过使用实验设计方法的短时注射毛细管电泳，针对抗阿尔茨海默氏病和抗真菌药的手性对映体分离通用策略。

  摘要：

  本研究描述了使用毛细管电泳（CE）方法手性拆分抗阿尔茨海默病药物（即多奈哌齐（DON），卡巴拉汀（RIV）和抗真菌药物，即酮康唑（KET），伊曲康唑（ITR））的通用策略，氟康唑（FLU）和舍他康唑（SRT），其中这些药物具有不同的碱性和酸性。几种改性的环糊精（CD）用于外消旋物的对映体分离，例如高度硫酸化的α，γCD，羟丙基-β-CD和磺丁基醚-β-CD。起始筛选条件包括pH值为2.5的50mM磷酸三乙醇胺缓冲液，施加的电压15 kV和温度25°C。在分离中实施的CE策略是从在进行实验设计的优化阶段之前进行筛选开始的。2）对这两个因素分别使用高，中和低值进行实验。对拟议策略的评估指出，使用低百分比的HS-γ-CD，五个外消旋体在pH 2.5时可获得最佳分离度，而SBE-β-CD是最成功的手性选择剂，可为所有六个外消旋体提供可接受的分离度在10分钟的运行时间内，在低pH值和％CD的情况下实现最佳分离

  DOI：

  10.1002/chir.22777

文献信息

• Steady-State Plasma Concentration of Donepezil Enantiomers and Its Stereoselective Metabolism and Transport In Vitro
  作者：Wan Lili、Guo Cheng、Zhou Zhiyong、Yu Qi、Li Yan、Li Dan、Zheng Xueli、Zhong Yuan

  DOI：10.1002/chir.22153

  日期：2013.9

  differences in the plasma concentration of two enantiomers of donepezil in Chinese patients with Alzheimer's disease (AD) and investigate in vitro stereoselective metabolism and transport. Donepezil enantiomers were separated and determined by LC‐MS/MS using D5‐donepezil as an internal standard on a Sepax Chiralomix SB‐5 column. In vitro stereoselective metabolism and transport of donepezil were investigated

  本研究的目的是阐明中国阿尔茨海默氏病（AD）患者中多奈哌齐的两种对映异构体血浆浓度的差异，并研究体外立体选择性代谢和转运。分离多奈哌齐对映异构体并通过LC-MS / MS在Sepax Chiralomix SB-5色谱柱上使用D5-多奈哌齐作为内标进行测定。在人肝微粒体和MDCKII-MDR1细胞单层中研究了多奈哌齐的体外立体选择性代谢和转运。确定了52例患者的给药前（Css-min）血浆浓度。（R）-多奈哌齐的平均血浆水平为14.94 ng / ml，（S）-多奈哌齐的平均血浆水平为23.37 ng / ml。一名患者的（R）-多奈哌齐血浆浓度高于（S）-多奈哌齐，比率为1.51。在51例患者中，（S）-多奈哌齐的平均血浆水平高于（R）-多奈哌齐的血浆水平，血浆（R）-（S）-多奈哌齐的比率在0.34至0.85之间变化。在体外微粒体系统中，（R）-多奈哌齐的降解速度快于（S）-多奈哌齐。（R）-多奈哌齐的V
• Organocatalyzed One‐Pot Sequential Deracemization of Aromatic Ketones Bearing a Tertiary Stereogenic Center
  作者：Claire Segovia、Jérémy Godemert、Jean‐François Brière、Vincent Levacher、Sylvain Oudeyer

  DOI：10.1002/adsc.202200857

  日期：2022.11.22

  stereogenic center at the α-position was achieved thanks to an acid-base strategy involving an enantioselective protonation reaction as a key step. This simple and efficient protocol yields enantioenriched ketones in up to 89% ee without the need to isolate sensitive intermediates such as silyl enolates. The key role of water in this process was underlined. This one-pot sequence constitutes a useful

  由于涉及对映选择性质子化反应作为关键步骤的酸碱策略，实现了在 α 位带有立体异构中心的芳香酮的有机催化一锅顺序去外消旋化。这种简单高效的方案可产生ee高达 89% 的对映体富集酮，而无需分离敏感的中间体，如甲硅烷基烯醇化物。强调了水在这一过程中的关键作用。这种一锅序列构成了对先前报道的化学驱动的氧化还原方案的有用扩展，从而增加了符合去外消旋化策略的分子面板。
• Sustained release formulations
  申请人：Ueki Yosuke

  公开号：US20070129402A1

  公开（公告）日：2007-06-07

  The invention provides sustained release formulations comprising donepezil, stereoisomers of donepezil, pharmaceutically acceptable salts of donepezil, or pharmaceutically acceptable salts of stereoisomers of donepezil. The formulations have desirable pharmacokinetic characteristics. Examples include AUC, Tmax, Cmax, dosage-corrected AUC, and dosage-corrected Cmax.
• Methods and compositions using cholinesterase inhibitors
  申请人：Ieni John

  公开号：US20080167343A1

  公开（公告）日：2008-07-10

  The invention provides methods for treating and/or preventing Alzheimer's disease, psychiatric illnesses, encephalitis, meningitis, fetal alcohol syndrome, Karsakoff's syndrome, anoxic brain injury, cardiopulmonary resuscitation injuries, diabetes, Sjogren's syndrome, mental retardation, developmental delay, menopause, strokes, macular degeneration, neuronal loss associated with macular degeneration, sleep disorders, severe Alzheimer's disease, jet lag, post-traumatic stress disorder, anxiety disorders, panic attacks, obsessive-compulsive disorder, amnesia, and other disorders by administering to a patient in need thereof at least one cholinesterase inhibitor. The invention also provides novel pharmaceutical compositions that can be administered to the eyes or to the nose of patients. In one embodiment, the cholinesterase inhibitor is donepezil, a stereoisomer thereof and/or a pharmaceutically acceptable salt thereof. In other embodiments, the cholinesterase inhibitor can be one or more of phenserine, tolserine, phenethylnorcymserine, ganstigmine, epastigmine, tacrine, physostigmine, pyridostigmine, neostigmine, rivastigmine, galantamine, citicoline, velnacrine, huperzine, metrifonate, heptastigmine, edrophonium, TAK-147, T-82, and upreazine.
• Cadasil Treatment with Cholinesterase Inhibitors
  申请人：Pratt Raymond

  公开号：US20080312189A1

  公开（公告）日：2008-12-18

  The invention provides methods for treating and/or preventing cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in a patient in need thereof by administering a therapeutically effective amount of at least one cholinesterase inhibitor. The invention also provides methods for treating and/or preventing neurovascular diseases caused by one or more mutations of the human Notch3 gene by administering a therapeutically effective amount of at least one cholinesterase inhibitor. In one embodiment, the cholinesterase inhibitor is donepezil, a stereoisomer thereof and/or a pharmaceutically acceptable salt thereof. The methods of the invention may further include administering a therapeutically effective amount of an HMG-CoA reductase inhibitor