科鲁西坦
描述
库鲁拉西坦，也称为其化学名称 N-(2,3-二甲基-5,6,7,8-四氢呋喃[2,3-b]喹啉-4-基)-2-(2-氧代-1-吡咯烷基)乙酰胺，是属于乙酰胺类家族的促智化合物。 它最初由三菱田边制药株式会社开发，用于治疗阿尔茨海默病，但现在已被广泛研究，以探索其在增强认知功能、记忆力和情绪方面的潜在益处 .
科学研究应用
库鲁拉西坦已被用于各种科学研究应用：
化学： 因其独特的化学结构及其形成新型衍生物的潜力而受到研究。
生物学： 探索其对神经递质系统，特别是乙酰胆碱的影响。
医学： 研究其治疗认知障碍、抑郁症和焦虑症的潜力.
工业： 用于开发旨在增强认知功能和情绪的促智补充剂。
作用机制
库鲁拉西坦主要增强高亲和力胆碱摄取 (HACU)，它是乙酰胆碱合成的限速步骤，乙酰胆碱是学习和记忆的重要神经递质 . 通过增加胆碱的可用性，库鲁拉西坦可促进乙酰胆碱的产生，从而增强认知功能。 它还调节胆碱转运蛋白调节系统，导致持久的促认知作用 .
类似化合物：
吡拉西坦： 第一个乙酰胺类促智药，以其增强认知的作用而闻名。
安奈西坦： 另一种具有抗焦虑和认知益处的乙酰胺类药物。
奥拉西坦： 以其兴奋作用和认知增强作用而闻名。
库鲁拉西坦的独特性： 库鲁拉西坦的独特性在于其增强高亲和力胆碱摄取的特定机制，这在其他乙酰胺类药物中未见。 这种独特的机制使其在改善胆碱能功能受损的疾病中的记忆力和学习方面特别有效 .
生化分析
Biochemical Properties
The primary mechanism of action for coluracetam is its ability to increase the uptake of choline into neurons . Choline is a precursor to the neurotransmitter acetylcholine, which plays a crucial role in cognitive processes such as memory formation, learning, and attention . Coluracetam achieves this by interacting with the high-affinity choline transporter (HACU), which is responsible for transporting choline across the cell membrane and into neurons . By enhancing the efficiency of the choline transport system, coluracetam promotes the synthesis and release of acetylcholine .
Cellular Effects
Coluracetam works mainly by increasing the levels of acetylcholine, a crucial neurotransmitter, and modulating choline uptake in the brain . Its unique mechanisms make it interesting for cognitive enhancement and potential therapeutic uses . Enhancement of Acetylcholine Synthesis: Coluracetam boosts acetylcholine synthesis . Acetylcholine is vital for learning and memory . The brain uses choline to produce acetylcholine . By enhancing this process, coluracetam improves cognitive functions .
Molecular Mechanism
Coluracetam enhances high-affinity choline uptake (HACU), which is the rate-limiting step of acetylcholine (ACh) synthesis . Studies have shown coluracetam to improve learning impairment on a single oral dose given to rats which have been exposed to cholinergic neurotoxins . Subsequent studies have shown that it may induce long-lasting procognitive effects in cholinergic neurotoxin-treated rats by changing the choline transporter regulation system .
Dosage Effects in Animal Models
Most of the research on coluracetam was done on animals rather than humans, so there are no universally accepted dosing guidelines . In a 2010 animal study, coluracetam improved artificially-induced memory deficits without producing any significant side effects .
Transport and Distribution
Coluracetam is fat-soluble, so it needs fats for optimal absorption . It’s usually taken sublingually (under the tongue) or orally . This method enhances its bioavailability .
Subcellular Localization
Given its mechanism of action, it is likely that coluracetam interacts with neurons in the brain where it enhances the uptake of choline, a precursor to the neurotransmitter acetylcholine .
Side effects and long-term safety remain areas requiring more comprehensive research .
准备方法
合成路线和反应条件： 库鲁拉西坦是通过一个多步骤过程合成的，该过程涉及 2,3-二甲基-5,6,7,8-四氢呋喃[2,3-b]喹啉与 2-氧代-1-吡咯烷基乙酰胺的反应。关键步骤包括：
喹啉核心的形成： 这涉及在受控条件下进行环化反应。
吡咯烷基的连接： 此步骤通常需要使用偶联试剂和催化剂来确保高产率和纯度。
工业生产方法： 库鲁拉西坦的工业生产遵循类似的合成路线，但规模更大。该过程针对效率、成本效益和遵守监管标准进行了优化。关键考虑因素包括：
反应可扩展性： 确保反应能够在不降低产率或纯度的情况下进行放大。
纯化： 采用结晶和色谱等技术，以达到所需的纯度水平。
化学反应分析
反应类型： 库鲁拉西坦会经历各种化学反应，包括：
氧化： 这可以在特定条件下发生，导致形成氧化衍生物。
还原： 还原反应可以改变官能团，可能改变化合物的活性。
取代： 取代反应可以引入不同的官能团，这些官能团可能增强或降低其促智特性。
常用试剂和条件：
氧化剂： 例如高锰酸钾或过氧化氢。
还原剂： 包括硼氢化钠或氢化铝锂。
催化剂： 通常用于取代反应中，以提高反应速度和产率。
主要产物： 这些反应的主要产物是库鲁拉西坦的修饰形式，它们可能具有不同的药理学特性。这些衍生物通常用于研究结构-活性关系。
相似化合物的比较
Piracetam: The first racetam nootropic, known for its cognitive-enhancing effects.
Aniracetam: Another racetam with anxiolytic and cognitive benefits.
Oxiracetam: Known for its stimulating effects and cognitive enhancement.
Uniqueness of Coluracetam: Coluracetam is unique due to its specific mechanism of enhancing high-affinity choline uptake, which is not observed in other racetams. This distinct action makes it particularly effective in improving memory and learning in conditions where cholinergic function is compromised .
属性
IUPAC Name |
N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-yl)-2-(2-oxopyrrolidin-1-yl)acetamide |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C19H23N3O3/c1-11-12(2)25-19-17(11)18(13-6-3-4-7-14(13)20-19)21-15(23)10-22-9-5-8-16(22)24/h3-10H2,1-2H3,(H,20,21,23) |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
PSPGQHXMUKWNDI-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CC1=C(OC2=NC3=C(CCCC3)C(=C12)NC(=O)CN4CCCC4=O)C |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C19H23N3O3 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID60159386 |
Source
|
| Record name | Coluracetam | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID60159386 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
341.4 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
CAS No. |
135463-81-9 |
Source
|
| Record name | Coluracetam | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=135463-81-9 | |
| Description | CAS Common Chemistry is an open community resource for accessing chemical information. Nearly 500,000 chemical substances from CAS REGISTRY cover areas of community interest, including common and frequently regulated chemicals, and those relevant to high school and undergraduate chemistry classes. This chemical information, curated by our expert scientists, is provided in alignment with our mission as a division of the American Chemical Society. | |
| Explanation | The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated. | |
| Record name | Coluracetam [INN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0135463819 | |
| Description | ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system. | |
| Record name | Coluracetam | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID60159386 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | COLURACETAM | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/V6FL6O5GR7 | |
| Description | The FDA Global Substance Registration System (GSRS) enables the efficient and accurate exchange of information on what substances are in regulated products. Instead of relying on names, which vary across regulatory domains, countries, and regions, the GSRS knowledge base makes it possible for substances to be defined by standardized, scientific descriptions. | |
| Explanation | Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required. | |
Retrosynthesis Analysis
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