扎那哌齐 | 142852-50-4

• 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: 扎那哌齐
• 中文别名: 3-(1-苄基哌嗪-4-)-1-(2,3,4,5-四氢-1H-苯并氮杂卓-8-)丙-1-酮
• 英文名称: Zanapezil
• 英文别名: 3-<1-(phenylmethyl)-4-piperidinyl>-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone；TAK-147；8-[1-oxo-3-[1-(phenylmethyl)piperidin-4-yl]propyl]-2,3,4,5-tetrahydro-1H-1-benzazepine；3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)propan-1-one
• CAS: 142852-50-4
• 化学式: C₂₅H₃₂N₂O
• 分子量: 376.542
• InChiKey: PMBLXLOXUGVTGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 储存条件：
  -20°C，密闭保存，干燥环境

制备方法与用途

扎那普利(TAK-147)是一种有效、可逆且选择性的乙酰胆碱酯酶(AChE)抑制剂。在大鼠大脑皮层匀浆中，扎那普利游离碱对乙酰胆碱酯酶活性具有显著的有效且可逆的抑制作用（IC50=51.2 nM）。此外，它还对毒蕈碱M1和M2受体有一定的结合抑制作用，Ki值分别为234 nM和340 nM。扎那普利游离碱在阿尔茨海默病(AD)早期阶段的研究中表现出应用潜力。

反应信息

• 作为反应物：
  描述：

  扎那哌齐 生成 1-Acetyl-8-[1-oxo-3-[1-(phenylmethyl)piperidin-4-yl]propyl]-2,3,4,5-tetrahydro-1H-1-benzazepine
  参考文献：
  名称：

  Condensed heterocyclic compounds, their production and use

  摘要：

  化学式（I）的一种缩合杂环衍生物：##STR1##其中X是氧原子、硫原子或R.sup.1--N<，其中R.sup.1是氢原子、可能被取代的碳氢基团或可能被取代的酰基团；R.sup.2是氢原子或可能被取代的碳氢基团；环A是可能被取代的苯环，k是0到3的整数；m是1到8的整数；n是1到6的整数，或其药学上可接受的盐，具有高胆碱酯酶抑制活性，并提供其制备方法。

  公开号：

  US05273974A1
• 作为产物：
  描述：

  3-(1-acetyl-4-piperidinyl)-1-(1-acetyl-2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone 在 盐酸 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 19.0h， 生成 扎那哌齐
  参考文献：
  名称：

  Central Cholinergic Agents. 6. Synthesis and Evaluation of 3-[1-(Phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)- 1-propanones and Their Analogs as Central Selective Acetylcholinesterase Inhibitors

  摘要：

  In an attempt to find central selective acetylcholinesterase (AChE) inhibitors, 3-[1-(phenyl-methyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanones 9 and their analogs were designed on the basis of our working hypothesis of the enzyme's active site. These compounds were prepared by regioselective Friedel-Crafts acylation of 2,3,4,5-tetrahydro-1H-benzazepines and related nitrogen heterocycles as a key step. Most compounds showed potent inhibitory activities with IC(50)s in the 10-300 nM range. In order to estimate their central selectivities, we examined their effects on the apomorphine-induced circling behavior in rats with unilateral striatal lesions. Among compounds with potent AChE inhibition, 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone fumarate (9a, TAK-147) (IC50 of AChE inhibition = 97.7 nM) inhibited the circling behavior at 3 mg/kg po, in which it had no significant effect on peripheral cholinergic effects. This demonstrates that 9a has favorable central selectivity. Furthermore, 9a significantly ameliorated diazepam-induced passive avoidance deficit at 1 mg/kg po. The benzazepine derivative 9a was selected as a candidate for clinical evaluation.

  DOI：

  10.1021/jm00041a007

文献信息

• Pharmaceutical preparation containing copolyvidone
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US10098866B2

  公开（公告）日：2018-10-16

  A stabilized preparation which comprises: a unstable drug in a polyethylene glycol-containing preparation; and a coating agent comprising a copolyvidone instead of polyethylene glycol with which the drug is coated.

  一种稳定的制剂，包括：在聚乙二醇含制剂中的不稳定药物；以及一种包衣剂，其包衣剂包括一种共聚维酮，而不是用聚乙二醇包衣药物。
• Direct β-Alkylation of Ketones and Aldehydes via Pd-Catalyzed Redox Cascade
  作者：Chengpeng Wang、Guangbin Dong

  DOI：10.1021/jacs.8b03530

  日期：2018.5.16

  report a direct β-alkylation of ketones and aldehydes with simple alkyl bromides through a Pd-catalyzed redox-cascade strategy. The use of a Cu cocatalyst is important for improved efficiency. The reaction is redox-neutral, without the need for strong acids or bases. Both cyclic and acyclic ketones, as well as α-branched aldehydes, are suitable substrates for coupling with secondary and tertiary alkyl

  我们报告了通过 Pd 催化的氧化还原级联策略用简单的烷基溴对酮和醛进行直接 β-烷基化。铜助催化剂的使用对于提高效率很重要。该反应是氧化还原中性的，不需要强酸或强碱。环状和无环酮以及α-支化醛都是与仲和叔烷基溴偶联的合适底物。Zanapezil 的简明正式合成是使用这种 β-烷基化方法实现的。
• Agents and crystals for improving excretory potency of urinary bladder
  申请人：——

  公开号：US20020177593A1

  公开（公告）日：2002-11-28

  Agents for improving potentcy of the urinary bladder which comprises an amine compound of non-carbamate-type having an acetylcholinesterase-inhibiting action. Particularly, crystals of a tricyclic, condensed, heterocyclic derivative are provided, which possess an excellent action to inhibit acetylcholine esterase and an action to improve the excretory potency of urinary bladder. As an example, crystals of of 8-[3-[1-[(3-fluorophenyl)-methyl]-4-piperidinyl]-1-oxopropyl]-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one or a salt thereof and pharmaceutical compositions containing them are disclosed.

  改善膀胱功能的药剂，包括一种非卡巴酯类胺化合物，具有乙酰胆碱酯酶抑制作用。特别地，提供了一种三环、紧凑、杂环衍生物的晶体，具有优异的抑制乙酰胆碱酯酶作用和改善膀胱排泄功能的作用。例如，揭示了8-[3-[1-[(3-氟苯基)-甲基]-4-哌啶基]-1-氧代丙基]-1,2,5,6-四氢-4H-吡咯烷[3,2,1-ij]-喹啉-4-酮或其盐和含有它们的药物组合物。
• Particulate construct comprising polyhydroxyalkanoate and method for producing it
  申请人：——

  公开号：US20030194443A1

  公开（公告）日：2003-10-16

  The invention provides a particulate construct such as microcapsules containing a drug, and serving a slow releasing preparation not associated with a practically unacceptable initial burst release but showing a practically acceptable zero-order release for a certain period and a producing method for such particulate construct, and a slow releasing preparation of a high drug content capable of stably incorporating the drug in the particulate construct such as microcapsules, and a producing method for such preparation. The invention also provides a particulate construct such as microcapsules utilizing a highly functional polymer compound and incorporating oil phase and/or water phase in solid phase, and a producing method therefor. Furthermore, the invention provides a particulate construct such as microcapsules having a hollow structure of a single polymer membrane as the outer shell and capable of containing many bubbles in the fine particles, and a producing method capable of preparing such construct with a high reproducibility. According to the invention, a particulate construct such as microcapsules is formed with polyhydroxyalkanoate of a specified structure and a drug for a desired purpose, an oil phase and/or a water phase, or a gaseous phase is included in such construct.

  本发明提供了一种微粒构造物，例如包含药物的微胶囊，用作缓释制剂，不会出现实际上不可接受的初始爆发释放，但在一定时间内显示实际上可接受的零级释放，并提供了这种微粒构造物的制备方法，以及能够稳定地将药物纳入微粒构造物中，例如微胶囊的高药物含量的缓释制剂，以及这种制备方法。本发明还提供了一种利用高功能聚合物化合物并将油相和/或水相纳入固相的微粒构造物，以及其制备方法。此外，本发明还提供了一种具有单一聚合物膜的空心结构的微粒构造物，能够在细小的颗粒中包含许多气泡，并提供了一种能够高度重复制备这种构造物的制备方法。根据本发明，可使用具有特定结构的聚羟基烷酸酯和药物制备微粒构造物，该构造物中包含油相和/或水相或气态相。
• Agents for improving excretory potency of urinary bladder
  申请人：——

  公开号：US20040116457A1

  公开（公告）日：2004-06-17

  Agents for improving excretory potency of the urinary bladder which comprises an amine compound of non-carbamate-type having an acetylcholinesterase-inhibiting action.

  改善排泄能力的尿道代理，包括一种非卡巴酯型胺类化合物，具有乙酰胆碱酯酶抑制作用。