ethyl 2-(5-bromopentyl)-5,6-dimethoxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate | 132219-01-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: ethyl 2-(5-bromopentyl)-5,6-dimethoxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate
• 英文别名: 2-(5-bromopentyl)-5,6-dimethoxy-1-oxo-indan-2-carboxylic acid ethyl ester；ethyl 2-(5-bromopentyl)-5,6-dimethoxy-1-indanone-2-carboxylate；ethyl 2-(5-bromopentyl)-5,6-dimethoxy-3-oxo-1H-indene-2-carboxylate
• CAS: 132219-01-3
• 化学式: C₁₉H₂₅BrO₅
• 分子量: 413.308
• InChiKey: QDOODMQYAHGBID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-(5-bromopentyl)-5,6-dimethoxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 44.0h， 生成 (5S)-5-{5-[(2RS)-5,6-dimethoxy-1-oxo-indan-2-yl]-pentylamino}-5,6,7,8-tetrahydro-1H-quinolin-2-one
  参考文献：
  名称：

  Design, synthesis and evaluation of novel heterodimers of donepezil and huperzine fragments as acetylcholinesterase inhibitors

  摘要：

  Four series of novel heterodimers comprised of donepezil and huperzine A (HupA) fragments were designed, synthesized, and evaluated in search of potent acetylcholinesterase (AChE) inhibitors as potential therapeutic treatment for Alzheimer's disease. Heterodimers comprised of dimethoxyindanone (from donepezil), hupyridone (from HupA), and connected with a multimethylene linker, were identified as potent and selective inhibitors of AChE. Diastereomeric heterodimers (RS,S)-17b (with a tetramethylene linker) exhibited the highest potency of inhibition towards AChE with an IC50 value of 9 nM and no detectable inhibitory effect on butyrylcholinesterase at 1 mM. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.044
• 作为产物：
  描述：

  5,6-二甲氧基茚酮 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 26.5h， 生成 ethyl 2-(5-bromopentyl)-5,6-dimethoxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate
  参考文献：
  名称：

  Design, synthesis and evaluation of novel heterodimers of donepezil and huperzine fragments as acetylcholinesterase inhibitors

  摘要：

  Four series of novel heterodimers comprised of donepezil and huperzine A (HupA) fragments were designed, synthesized, and evaluated in search of potent acetylcholinesterase (AChE) inhibitors as potential therapeutic treatment for Alzheimer's disease. Heterodimers comprised of dimethoxyindanone (from donepezil), hupyridone (from HupA), and connected with a multimethylene linker, were identified as potent and selective inhibitors of AChE. Diastereomeric heterodimers (RS,S)-17b (with a tetramethylene linker) exhibited the highest potency of inhibition towards AChE with an IC50 value of 9 nM and no detectable inhibitory effect on butyrylcholinesterase at 1 mM. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.044

文献信息

• Central Cholinergic Agents. IV. Synthesis and Acetylcholinesterase Inhibitory Activities of .OMEGA.-(N-Ethyl-N-(phenylmethyl)amino)-1-phenyl-1-alkanones and Their Analogues with Partial Conformational Restriction.
  作者：Yuji ISHIHARA、Masaomi MIYAMOTO、Takahiro NAKAYAMA、Giichi GOTO

  DOI：10.1248/cpb.41.529

  日期：——

  Inhibitors of acetylcholinesterase (AChE) have been designed based on a working hypothesis of the enzyme's active site. These compounds were tested for their inhibitory activities on AChE and ω-[N-ethyl-N-(phenylmethyl)amino]-1-phenyl-1-alkanones (3) were found to be potent inhibitors. Various analogues of 3 were prepared to study the effect on AChE inhibition of partial restriction of conformation. Compounds with potent AChE inhibition were further evaluated in terms of central selectivity : the ratio of central action (ameliorationg effect on scopolamine-induced memory impairment using a T-maze alternation task) to peripheral action.

  乙酰胆碱酯酶（AChE）抑制剂的设计是基于酶的活性位点的工作假设。这些化合物被测试了其对AChE的抑制活性，ω-[N-乙基-N-(苯甲基)氨基]-1-苯基-1-烷酮（3）被发现是有效的抑制剂。为了研究构象部分限制对AChE抑制的影响，制备了3的各种类似物。具有强效AChE抑制的化合物进一步评估了其中心选择性：中心作用（在T型迷宫交替任务中改善斯科波拉明诱导的记忆损害的效果）与外周作用的比率。
• Aralkylamine compounds
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05180746A1

  公开（公告）日：1993-01-19

  An aralkylamine compound of the formula ##STR1## wherein R.sup.1 means a hydrogen atom or a lower alkyl group; R.sup.2 means an aromatic group which may be substituted; R.sup.3 means a hydrogen atom, a lower alkyl group or an aromatic group which may be substituted; n means an integer of 0 to 7; ring A means a five-through eight-membered cyclic group which may be substituted and may contain one or two hetero atom(s) of O and S atoms as the ring-constituents; and ring B means a benzene ring which may be substituted, or a salt thereof, which is useful as an cholinesterase inhibitor and a cerebral function ameliorating agent.

  化合物的化学式为##STR1## 其中R1表示氢原子或低碳基; R2表示可以被取代的芳香基团; R3表示氢原子，低碳基或可以被取代的芳香基团; n表示0到7的整数; 环A表示可以被取代的五到八元环，并且可以包含一个或两个O和S原子作为环构成部分; 环B表示可以被取代的苯环，或其盐，其可用作胆碱酯酶抑制剂和改善脑功能的药物。
• US5180746A
  申请人：——

  公开号：US5180746A

  公开（公告）日：1993-01-19
• Design, synthesis and evaluation of novel heterodimers of donepezil and huperzine fragments as acetylcholinesterase inhibitors
  作者：Yueqing Hu、Jun Zhang、Oormila Chandrashankra、Fanny C.F. Ip、Nancy Y. Ip

  DOI：10.1016/j.bmc.2012.11.044

  日期：2013.2

  Four series of novel heterodimers comprised of donepezil and huperzine A (HupA) fragments were designed, synthesized, and evaluated in search of potent acetylcholinesterase (AChE) inhibitors as potential therapeutic treatment for Alzheimer's disease. Heterodimers comprised of dimethoxyindanone (from donepezil), hupyridone (from HupA), and connected with a multimethylene linker, were identified as potent and selective inhibitors of AChE. Diastereomeric heterodimers (RS,S)-17b (with a tetramethylene linker) exhibited the highest potency of inhibition towards AChE with an IC50 value of 9 nM and no detectable inhibitory effect on butyrylcholinesterase at 1 mM. (C) 2012 Elsevier Ltd. All rights reserved.