aminolupinane | 2346-98-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹嗪类
• 英文名称: aminolupinane
• 英文别名: (1R,9aR)-1-(chloromethyl)-octahydro-2H-quinolizine；(1S,9aR)-(octahydro-2H-quinolizin-1-yl)methylamine；[(1S,9aR)-Octahydro-2H-quinolizin-1-ylmethyl]amine；1-(aminomethyl)octahydro-(1S,9aR)-2H-quinolizine；(1S,9aR)-octahydro-2H-quinolizine-1-methanamine；(-)-aminolupinane；[(1S,9aR)-2,3,4,6,7,8,9,9a-octahydro-1H-quinolizin-1-yl]methanamine
• CAS: 2346-98-7；10248-19-8；15527-89-6；22342-32-1；46000-58-2；75532-84-2；145842-67-7
• 化学式: C₁₀H₂₀N₂
• 分子量: 168.282
• InChiKey: WSBDCEJEINRUML-VHSXEESVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 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：

  aminolupinane 在 palladium on activated charcoal 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 0.08h， 生成 4-(acetylamino)-N-[(1S,9aR)-octahydro-2H-quinolizin-1-ylmethyl]benzamide
  参考文献：
  名称：

  Novel Quinolizidinyl Derivatives as Antiarrhythmic Agents

  摘要：

  Eighteen analogues of lidocaine, mexiletine, and procainamide were synthesized, replacing their aminoalkyl chains with the rigid and cumbersome quinolizidine nucleus. The target compounds were tested for antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig (gp) heart tissues and to assess calcium antagonist activity. Most compounds exhibited from moderate to high antiarrhythmic activity, and compounds 7, 9, and 19 were more active and potent than quinidine and lidocaine, while producing only modest inotropic, chronotropic, and vasorelaxant effects. These compounds were studied on spontaneously beating Langendorff-perfused gp heart. While quinidine and amiodarone produced a dose-dependent prolongation of all the ECG intervals, compounds 7, 9, and 19, even at concentrations 10-20 times higher than EC50 for the antiarrhythmic activity, only moderately prolonged the PR and QT intervals, leaving unchanged the QRS complex. Ether 7 deserves further investigations due to its interesting cardiovascular profile.

  DOI：

  10.1021/jm060878m
• 作为产物：
  描述：

  羽扇豆宁 在 氨 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 30.0h， 生成 aminolupinane
  参考文献：
  名称：

  (-)-Epilamprolobine 和它的 N-氧化物，来自 Sophora tomentosa 的羽扇豆生物碱

  摘要：

  摘要 从毛刺槐鲜叶中进一步分离到了三种新型羽扇豆生物碱，(-)-epilamprolobine、(+)-epilamprolobine N-oxide 和 5-(3′-甲氧羰基丁酰基)aminomethyl-trans-quinolizidine N-oxide。连同 (+)-苦参碱、(+)-苦参碱 N-氧化物、(+)-槐果碱 N-氧化物、(-)-anagyrine、(-)- baptifoline、(-)-胞嘧啶、(-)- N-甲基胞嘧啶、(-)- N-甲酰胞嘧啶、(-)- N-乙酰胞嘧啶和(±)-ammodendrine。(+)-epilamprolobine N-oxide (1 R :5 R :6 S ) 和 (-)-epilamprolobine (5 R :6 S ) 的绝对构型也已通过光谱数据和与合成 (+) 的比较确定-epilamprolobine (5 S :6 R )

  DOI：

  10.1016/s0031-9422(00)98564-9

文献信息

• Quinolizidinyl derivatives of bi- and tricyclic systems as potent inhibitors of acetyl- and butyrylcholinesterase with potential in Alzheimer’s disease
  作者：B. Tasso、M. Catto、O. Nicolotti、F. Novelli、M. Tonelli、I. Giangreco、L. Pisani、A. Sparatore、V. Boido、A. Carotti、F. Sparatore

  DOI：10.1016/j.ejmech.2011.02.071

  日期：2011.6

  6-hydroxycoumarin an inverted selectivity for acetylcholinesterase (AChE) was observed (e.g. 46: IC50 versus AChE = 0.35 μM; SI = 0.06). Docking studies furnished a sound interpretation of the observed different enzyme activity. Several of the studied compounds have shown, in the past, additional pharmacological properties (as antagonism on presynaptic muscarinic autoreceptor; inhibition of enkephaline aminopeptidase

  在强效和选择性丁酰胆碱酯酶（BChE）抑制剂Ethopropazine和Astra1397的模式上，研究了双环和三环（杂）芳族系统的喹喔啉基衍生物对偶或BChE选择性抑制剂。所有化合物均显示出对两种胆碱酯酶的活性，但对BChE的抑制作用通常更强，大多数化合物的亚微摩尔IC 50值（例如15：IC 50 对BChE = 0.15μM； SI = 47）。但是，在6-羟基香豆素的喹唑啉基衍生物的一个子集中，观察到了对乙酰胆碱酯酶（AChE）的反向选择性（例如，46：IC 50 与AChE = 0.35μM; SI = 0.06）。对接研究对观察到的不同酶活性提供了很好的解释。过去，一些研究过的化合物显示出与阿尔茨海默氏病有关的其他药理特性（如对突触前毒蕈碱型自身受体的拮抗作用；对脑啡肽氨基肽酶的抑制作用和抗精神病活性），因此可能代表了一些有趣的疾病的发展热点。单实体多目标药物。
• Novel amodiaquine congeners as potent antimalarial agents
  作者：Manolo Casagrande、Nicoletta Basilico、Silvia Parapini、Sergio Romeo、Donatella Taramelli、Anna Sparatore

  DOI：10.1016/j.bmc.2008.05.068

  日期：2008.7

  To develop new classes of antimalarial agents, the possibility of replacing the phenolic ring of amodiaquine, tebuquine, and isoquine with other aromatic nuclei was investigated. Within a first set of pyrrole analogues, several compounds displayed high activity against both D10 (CQ-S) and W-2 (CQ-R) strains of Plasmodium falciparum. The isoquine structure was also modified by replacing the diethylamino

  为了开发新的抗疟剂，研究了用其他芳香核取代氨二喹，戊丁喹和异喹的酚环的可能性。在第一批吡咯类似物中，几种化合物对恶性疟原虫的D10（CQ-S）和W-2（CQ-R）菌株均显示高活性。还通过用代谢上更稳定的双环部分取代二乙氨基并用氯原子取代芳族羟基官能团来修饰异喹啉结构。在这些化合物中，两种喹唑并二甲基甲氨基衍生物（6f和7f）对CQ-S和CQ-R菌株均显示出高活性。
• [EN] PROTEIN KINASE C INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE LA PROTÉINE KINASE C ET UTILISATIONS DE CEUX-CI
  申请人：RIGEL PHARMACEUTICALS INC

  公开号：WO2014089112A1

  公开（公告）日：2014-06-12

  This disclosure concerns compounds which are useful as inhibitors of protein kinase C (PKC) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC. This disclosure also relates to pharmaceutical compositions that include these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  这份披露涉及一些化合物，它们可作为蛋白激酶C（PKC）的抑制剂，因此可用于治疗通过PKC的活性介导或维持的各种疾病和疾病。这份披露还涉及包括这些化合物的药物组合物，使用这些化合物治疗各种疾病和疾病的方法，制备这些化合物的过程以及在这些过程中有用的中间体。
• Synthesis and comparison of antiplasmodial activity of (+), (−) and racemic 7-chloro-4-(N-lupinyl)aminoquinoline
  作者：Chiara Rusconi、Nadia Vaiana、Manolo Casagrande、Nicoletta Basilico、Silvia Parapini、Donatella Taramelli、Sergio Romeo、Anna Sparatore

  DOI：10.1016/j.bmc.2012.07.041

  日期：2012.10

  issue, the corresponding racemic compound, derived from synthetic (±)-lupinine was considered a cheaper alternative for the development of a novel antimalarial agent. Therefore, the racemic and the 7-chloro-4-(N-(+)-lupinyl)aminoquinoline ((±)-AM-1; (+)-AM-1) were synthesized and their in vitro antimalarial activity and cytotoxicity compared with those of (−)-AM-1. The (+)-lupinine required for the synthesis

  最近Ñ - （ - ） - lupinyl衍生物7-氯-4-氨基喹啉的（（ - ） - AM-1; 7-氯-4- ñ - [（1-小号，9A ř）（八氢-2 ħ -喹啉嗪-1-基）甲基]氨基}喹啉对恶性疟原虫的氯喹敏感和耐药菌株均显示出有效的体外和体内活性。然而，（-）-AM-1是从（-）-羽扇豆碱（一种从羽扇豆羽扇豆中分离出来的昂贵生物碱）开始合成的目前，其全球产量不足以满足大型市场的需求。为了克服这个问题，衍生自合成（±）-羽扇豆碱的相应外消旋化合物被认为是开发新型抗疟药的廉价替代品。因此，合成了外消旋和7-氯-4-（N -（+）-羽扇豆基）氨基喹啉（（±）-AM-1;（+）-AM-1），并比较了它们的体外抗疟活性和细胞毒性。 （-）-AM-1的那些。合成（+）-AM-1所需的（+）-羽扇豆碱是通过先前未描述的脂肪酶催化的（±）-羽扇豆碱的动力学拆分而获得的。就抗疟疾活性而言，（±
• Modified Coumarins. 35. Synthesis of Coumarins Containing a Lupinine Moiety
  作者：Yu. A. Nikitina、A. I. Galaev、Ya. L. Garazd、M. M. Garazd、V. G. Kartsev

  DOI：10.1007/s10600-016-1545-3

  日期：2016.1

  New coumarin derivatives containing a lupinine moiety were prepared via amidation of coumarinyloxyacetic, coumarinylacetic, and coumarinylpropionic acids by lupinamine.

  通过羽扇豆胺对香豆素氧乙酸、香豆素乙酸和香豆素丙酸的酰胺化作用，制备出了含有羽扇豆碱分子的新型香豆素衍生物。