5-(3,4-dihydroisoquinolin-2(1H)-yl)pentan-1-amine | 221196-24-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 5-(3,4-dihydroisoquinolin-2(1H)-yl)pentan-1-amine
• 英文别名: 5-(3,4-dihydro-1H-isoquinolin-2-yl)pentan-1-amine
• CAS: 221196-24-3
• 化学式: C₁₄H₂₂N₂
• 分子量: 218.342
• InChiKey: ZNYDJYHCKBOCOU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(3,4-dihydroisoquinolin-2(1H)-yl)pentan-1-amine 在 盐酸 、 potassium carbonate 作用下， 以 二氯甲烷 、 异丙醇 、 乙腈 为溶剂， 反应 48.0h， 生成 5-(3,4-dihydroisoquinolin-2(1H)-yl)-N,N-diethylpentan-1-amine dihydrochloride
  参考文献：
  名称：

  靶向胆碱酯酶和淀粉样蛋白 β 的新型异二聚体、多配体的合成、分子建模和生物学评价

  摘要：

  胆碱酯酶和淀粉样蛋白 β 是寻找新的有效治疗阿尔茨海默病的主要生物学靶标之一。该研究描述了设计为双结合位点乙酰胆碱酯酶抑制剂的新化合物的合成和药理学评价。在合成的化合物中，有两个值得特别关注——化合物 42 和 13。前者是一种糖精衍生物，也是最有效和选择性的乙酰胆碱酯酶抑制剂 (EeAChE IC50 = 70 nM)。Isoindoline-1,3-dione 衍生物 13 对乙酰胆碱酯酶和丁酰胆碱酯酶 (BuChE) 显示出平衡的抑制效力（EeAChE IC50 = 0.76 μM，EqBuChE IC50 = 0.618 μM），并在 10 μM 时抑制淀粉样蛋白聚集（35.8%）。动力学研究表明，开发的化合物可作为混合或非竞争性乙酰胆碱酯酶抑制剂。根据分子模型研究，它们能够与乙酰胆碱酯酶的催化活性位点和外周活性位点相互作用。它们穿过血脑屏障 (BBB) 的能力在体外平行人工膜通透性

  DOI：

  10.3390/molecules21040410
• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 5-(3,4-dihydroisoquinolin-2(1H)-yl)pentan-1-amine
  参考文献：
  名称：

  D₂ Dopamine Receptor G Protein-Biased Partial Agonists Based on Cariprazine

  摘要：

  Functionally selective G protein-coupled receptor ligands are valuable tools for deciphering the roles of downstream signaling pathways that potentially contribute to therapeutic effects versus side effects. Recently, we discovered both G(i/o)-biased and beta-arrestin2-biased D-2 receptor agonists based on the Food and Drug Administration (FDA)-approved drug aripiprazole. In this work, based on another FDA-approved drug, cariprazine, we conducted a structure-functional selectivity relationship study and discovered compound 38 (MS1768) as a potent partial agonist that selectively activates the G(i/o) pathway over beta-arrestin2. Unlike the dual D2R/D3R partial agonist cariprazine, compound 38 showed selective agonist activity for D2R over D3R. In fact, compound 38 exhibited potent antagonism of dopamine-stimulated beta-arrestin2 recruitment. In our docking studies, compound 38 directly interacts with S193(5.42) on TM5 but has no interactions with extracellular loop 2, which appears to be in contrast to the binding poses of D2R beta-arrestin2-biased ligands. In in vivo studies, compound 38 showed high D2R receptor occupancy in mice and effectively inhibited phencyclidine-induced hyperlocomotion.

  DOI：

  10.1021/acs.jmedchem.9b00508

文献信息

• SAR Matrices Enable Discovery of Mixed Efficacy μ-Opioid Receptor Agonist Peptidomimetics with Simplified Structures through an Aromatic-Amine Pharmacophore
  作者：Sean Henry、Jessica P. Anand、Ashley C. Brinkel、Douglas M. McMillan、Jack. J. Twarozynski、Christian E. Loo、John R. Traynor、Henry I. Mosberg

  DOI：10.1021/acschemneuro.0c00693

  日期：2021.1.6

  effective analgesics with reduced side effects. In this series, a tetrahydroquinoline (THQ) or substituted phenyl is employed to link two key pharmacophore elements, a dimethyltyrosine amino acid and typically an aromatic pendant. Using new and previously reported analogues, we constructed a structure–activity relationship (SAR) matrix that probes the utility of previously reported amine pendants. This

  我们之前描述了有效的 μ-阿片受体 (MOR)-激动剂/δ-阿片受体 (DOR)-拮抗剂拟肽配体的开发，作为一种减少副作用的有效镇痛药的方法。在该系列中，四氢喹啉 (THQ) 或取代的苯基用于连接两个关键的药效团元素，即二甲基酪氨酸氨基酸和通常的芳香族侧链。使用新的和以前报道的类似物，我们构建了一个构效关系 (SAR) 矩阵，用于探索以前报道的胺悬垂物的效用。该矩阵表明，当使用四氢异喹啉 (THIQ) 悬垂物时，尽管去除了核心苯环上的取代基，但这些配体的 MOR 激动剂/DOR 拮抗剂特性不会改变。基于这一观察，我们保留了 THIQ 吊坠，并用更简单的脂肪链结构取代了苯基核心。这些更简单的类似物被证明是有效的 MOR 激动剂，它们对 DOR 和 κ-阿片受体 (KOR) 的影响具有高度可变性。这些数据表明，THIQ 悬垂物的胺可能是一种有利于高 MOR 功效的新型药效团元素，而 THIQ 悬垂物的芳环可能产生高
• Aminopyridazines as Acetylcholinesterase Inhibitors
  作者：Jean-Marie Contreras、Yveline M. Rival、Said Chayer、Jean-Jacques Bourguignon、Camille G. Wermuth

  DOI：10.1021/jm981101z

  日期：1999.2.1

  Following the discovery of the weak, competitive and reversible acetylcholinesterase (AChE)-inhibiting activity of minaprine (3c) (IC50 = 85 microM on homogenized rat striatum AChE), a series of 3-amino-6-phenylpyridazines was synthesized and tested for inhibition of AChE. A classical structure-activity relationship exploration suggested that, in comparison to minaprine, the critical elements for high

  发现米那匹林（3c）的弱，竞争性和可逆性乙酰胆碱酯酶（AChE）抑制活性（对均质大鼠纹状体AChE的IC50 = 85 microM）后，合成了一系列3-氨基-6-苯基哒嗪并测试了其抑制作用AChE。一项经典的构效关系研究表明，与米萘普林相比，高乙酰胆碱酯酶抑制的关键因素如下：（i）中央哒嗪环的存在；（ii）亲脂性阳离子头的必要性；（iii）改变哒嗪环与阳离子头之间的碳原子数为2至4-5。在研究的所有衍生物中，3- [2-（1-苄基哌啶-4-基）乙基氨基] -6-苯基哒嗪（3y）在纯化的AChE（电鳗）上的IC50为0.12 microM，
• 5-HT7 receptor antagonists
  申请人：Torrens Jover Antoni

  公开号：US20060040978A1

  公开（公告）日：2006-02-23

  The invention relates to compounds having pharmacological activity towards the 5-HT7 receptor, and more particularly to some tetrahydroisoquinoline substituted sulfonamide compounds, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use for the treatment and or prophylaxis of a disease in which 5-HT is involved, such as CNS disorders.

  这项发明涉及具有对5-HT7受体具有药理活性的化合物，更特别地涉及一些四氢异喹啉取代磺胺基化合物，以及制备这些化合物的过程，包括含有它们的药物组合物，并且用于治疗和/或预防涉及5-HT的疾病，如中枢神经系统紊乱。
• Discovery of Tryptophan‐tetrahydroisoquinoline Derivatives as Multifunctional Agents for Treatment of Alzheimer's Disease
  作者：Xin Lu、Yijun Liu、Nan Qin、Chenxi Du、Yanyu Hu、Yao Chen、Haopeng Sun

  DOI：10.1002/cjoc.202200096

  日期：2022.8

  The cholinesterases are essential targets implicated in the pathogenesis of Alzheimer's disease (AD). We have identified tryptophan-tetrahydroisoquinoline derivatives as selective micro-nanomolar butyrylcholinesterase (BChE) inhibitors. Molecular docking was applied for the rational design and binding mode analysis. They were defined according to their target inhibitory activity, low cytotoxicity,

  胆碱酯酶是涉及阿尔茨海默病 (AD) 发病机制的重要靶标。我们已将色氨酸-四氢异喹啉衍生物鉴定为选择性微纳摩尔丁酰胆碱酯酶 (BChE) 抑制剂。分子对接用于合理设计和结合模式分析。它们是根据它们的目标抑制活性、低细胞毒性、预测的通过血脑屏障 (BBB) 的渗透性和体内认知改善来定义的。此外，优选的化合物显示出降低自身诱导的 Aβ 1-42聚集和 Aβ 1-42诱导的 SH-SY5Y 细胞损伤的能力。总之，这些因素表明它们具有作为 AD 治疗独特先导化合物的潜力。
• 5-ht7 receptor antagonists
  申请人：Torrens Jover Antoni

  公开号：US20090163542A1

  公开（公告）日：2009-06-25

  The invention relates to compounds having pharmacological activity towards the 5-HT7 receptor, and more particularly to some tetrahydroisoquinoline substituted sulfonamide compounds, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use for the treatment and or prophylaxis of a disease in which 5-HT is involved, such as CNS disorders.