+-八角枫碱 | 34366-21-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 中文名称: +-八角枫碱
• 英文名称: (R)-(+)-anabasine
• 英文别名: (R)-3-(Piperidin-2-YL)pyridine；3-[(2R)-piperidin-2-yl]pyridine
• CAS: 34366-21-7
• 化学式: C₁₀H₁₄N₂
• 分子量: 162.235
• InChiKey: MTXSIJUGVMTTMU-SNVBAGLBSA-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：
  0.5
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

在体外，大鼠、兔和豚鼠对(-)-毒藜碱的代谢产生了(-)-毒藜碱，后者被代谢为1'-N-羟基毒藜碱和毒藜碱1'DELTA-亚硝基。加固的肺微粒体组分的代谢产物相似。

IN VITRO METABOLISM OF (-)-METHYLANABASINE BY RAT, RABBIT & GUINEA PIG GAVE (-)-ANABASINE WHICH WAS METABOLIZED TO 1'-N-HYDROXYANABASINE & ANABASINE 1'DELTA-NITRONE. METABOLIC PRODUCTS OF FORTIFIED LUNG MICROSOMAL FRACTIONS WERE SIMILAR.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 副作用

神经毒素 - 其他中枢神经系统神经毒素

Neurotoxin - Other CNS neurotoxin

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 相互作用

增强剂，抑制人类血小板的血清素摄取。

ANABASINE ENHANCED SEDATIVE ACTION OF RESERPINE, APOMORPHINE, & 5-HYDROXYTRYPTOPHAN IN FROGS & INHIBITED SEROTONIN UPTAKE BY HUMAN THROMBOCYTES.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道。如有必要，进行吸痰。可能需要积极的气道管理。注意呼吸不足的迹象，如有必要，协助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。预期可能出现癫痫，并在必要时进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在转运过程中，用生理盐水连续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释。给予活性炭……。/尼古丁及相关化合物/

/SRP:/ Basic treatment: Establish a patent airway. Suction if necessary. Aggressive airway management may be needed. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Anticipate seizures and treat if necessary... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Nicotine and Related Compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识或呼吸停止的患者，考虑进行口咽或鼻咽气管插管以控制气道。监测心率和必要时治疗心律失常... . 使用D5W开始静脉输液 /SRP: "保持开放"，最低流量/. 如果出现低血容量的迹象，使用乳酸钠林格液。注意液体过载的迹象。用地西泮治疗癫痫... . 使用丙美卡因氢氯化物协助眼部冲洗... . /尼古丁及相关化合物/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or in respiratory arrest. Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Treat seizures with diazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Nicotine and Related Compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

症状学：1. 口腔和喉咙有灼热感，流涎，恶心，腹痛，呕吐，腹泻。胃肠道反应较轻，但在皮肤和呼吸道暴露后确实会发生。/尼古丁/

SYMPTOMATOLOGY: 1. BURNING SENSATION IN MOUTH & THROAT, SALIVATION, NAUSEA, ABDOMINAL PAIN, VOMITING, DIARRHEA. GI REACTIONS ARE LESS SEVERE BUT DO OCCUR AFTER CUTANEOUS & RESP EXPOSURES. /NICOTINE/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

尼古丁很容易通过皮肤和粘膜被吸收。

Anabasine is readily absorbed from the skin and from mucous membranes.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  +-八角枫碱 在 水 、 三氟乙酸 作用下， 以 乙醇 为溶剂， 反应 13.33h， 生成
  参考文献：
  名称：

  Microwave-mediated reactions of 3-aminomethylpyridines with acetylenedicarboxylates. A novel synthetic route to dihydronaphthyridines and naphthyridine-1-ones

  摘要：

  Reaction of 3-(1-alkylamino)pyridines with electron deficient acetylenes in the presence of acids yields 1,2-dihydro-[2,7]naphthyridine-3,4-dialkyldicarboxylates 4 in 35-72% yield. Compounds 4 unsubstituted in position 1 can be easily oxidized with potassium permanganate into the respective naphthyridine-1-ones derivatives 5 in good yields. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2005.04.053
• 作为产物：
  描述：

  N-allyl-1-(pyridin-3-yl)but-3-en-1-amine 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 盐酸 、 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 +-八角枫碱
  参考文献：
  名称：

  双功能高烯丙胺的合成修饰：2-芳基哌啶、(R)-anatabine 和 (R)-anabasine 的合成

  摘要：

  摘要 具有正交双功能手柄、胺和侧链烯丙基单元的手性高烯丙基胺可以很容易地转化为 N-杂环。N-烯丙基化和 Ru 催化的闭环复分解分三步提供具有生物活性的 2-芳基哌啶、烟草生物碱 (R)-anatabine 和 (R)-anabasine。(R)-N-methylanatabine 和 (R)-N-methylanabasine 的正式合成也已完成。图形概要

  DOI：

  10.1080/00397911.2019.1643890

文献信息

• Synthesis, characterization and anticancer evaluation of nitrogen-substituted 1-(3-aminoprop-1-ynyl)-4-hydroxyanthraquinone derivatives
  作者：Nafisa S. Sirazhetdinova、Victor A. Savelyev、Dmitry S. Baev、Tatyana S. Golubeva、Lyubov S. Klimenko、Tatyana G. Tolstikova、Jamsranjav Ganbaatar、Elvira E. Shults

  DOI：10.1007/s00044-021-02754-1

  日期：2021.8

  (A3-coupling) of the new 1-ethynyl-4-hydroxyanthraquinone with secondary amines and formaldehyde was the main approach for the synthesis of nitrogen-substituted 1-[3-(amino)prop-1-ynyl]-4-hydroxyanthraquinones. The influence of different substituents in the amine on reaction rate and yield has been evaluated. The cytotoxicity of 1-ethynyl-4-hydroxyanthraquinones was assessed using the conventional MTT assay

  蒽醌类化合物因其生物活性、着色特性和合成应用而备受关注。在这里，我们描述了一种温和方便的方法来修饰 1-乙炔基-4-羟基蒽醌，该方法是从1-羟基-4-碘蒽醌与炔烃的Sonogashira交叉偶联反应中获得的。铜(I)催化的一锅三组分反应(A 3-偶联）新的 1-乙炔基-4-羟基蒽醌与仲胺和甲醛是合成氮取代的 1-[3-（氨基）丙-1-炔基]-4-羟基蒽醌的主要方法。已评估胺中不同取代基对反应速率和产率的影响。1-ethynyl-4-hydroxyanthraquinones 的细胞毒性使用常规 MTT 测定法进行评估。中合成的所有化合物，蒽醌衍生物炔丙胺28，29，30，和34具有朝向成胶质细胞瘤肿瘤细胞的最有希望的细胞毒性潜力; 化合物14和19显示出对前列腺癌细胞 DU-145 和18 的选择性, 24 — 在乳腺癌细胞系 MCF-7 上。化合物18和24对这些癌细胞的生长抑制与标准药物多柔比星的抑制相当。对
• Niobium-Catalyzed Highly Enantioselective Aza-Diels–Alder Reactions
  作者：Václav Jurčík、Kenzo Arai、Matthew M. Salter、Yasuhiro Yamashita、Shū Kobayashi

  DOI：10.1002/adsc.200700615

  日期：2008.3.25

  Niobium-based chiral Lewis acid was found to be highly effective catalyst for aza-Diels–Alder reactions of imines with Danishefsky‘s dienes. The reactions proceed in high yield with high enantioselectivity for both aromatic and aliphatic imines. The developed methodology was applied to total synthesis of (+)-anabasine.

  铌基手性路易斯酸被发现是亚胺与Danishefsky二烯的氮杂Diels-Alder反应的高效催化剂。对于芳族和脂族亚胺，反应以高对映选择性和高收率进行。所开发的方法应用于（+）-天麻碱的全合成。
• Synthesis of New Conjugates of Coumarins with Anabasine and Cytisine
  作者：S. P. Bondarenko、G. P. Mrug、V. I. Vinogradova、M. S. Frasinyuk

  DOI：10.1007/s10600-021-03268-3

  日期：2021.1

  with glycidyl ethers of 3-arylcoumarins were studied. A series of cytisine–coumarin conjugates were synthesized via regiospecific opening of the oxirane ring by cytisine. Methods for conjugating anabasine and cytisine with 3-arylcoumarins through a but-2-ynyl linker via reactions of propargyl ethers of 7-hydroxy- and 6-hydroxy-3-arylcoumarins with the alkaloids were proposed.

  研究了胞苷与3-芳基香豆素缩水甘油醚的反应。通过胞嘧啶对环氧乙烷环的区域特异性打开，合成了一系列胞嘧啶-香豆素偶联物。提出了通过 7-羟基-和 6-羟基-3-芳基香豆素的炔丙基醚与生物碱的反应，通过but-2-ynyl 接头将anabasine 和cytisine 与3-芳基香豆素缀合的方法。
• Ligands that target Plasmodium sporozoite binding sites on CD81 and therapeutic methods using them
  申请人：American University In Cairo (AUC)

  公开号：US10548895B2

  公开（公告）日：2020-02-04

  The invention pertains to ligands that bind to CD81 and that inhibit or block Plasmodium attachment to CD81, compositions and methods for preventing, inhibiting or treating infection by Plasmodium and ligands that target a Plasmodium binding site on CD81 and methods of making and using them. A series of ligand binding sites on the large extracellular loop of the open conformation of CD81 have been identified. Several important sites were located in regions identified by mutational studies to be the site of Plasmodium binding. Ligands that recognize these sites were identified. Linking together two or three ligands that bind with low or moderate affinities to different structurally unique sites on a target protein were used to generate small molecule ligand conjugates that exhibit very high affinities to their CD81 targets. Hybrid ligand molecules were also designed using fragment-based drug design methods to generate analogs of the ligands that bind more tightly to the protein than the parent compounds. Identification and design of groups of compounds that bind to CD81 for use as therapeutics for treating patients infected by Plasmodium and pathogens that interact with CD81. By binding to CD81, these molecules can block 1) Plasmodium attachment and entry into cells (infection), especially hepatocytes; 2) block or inhibit inflammatory responses caused by Plasmodium, and 3) block or inhibit the induction of other pathologies associated with Plasmodium infection.

  本发明涉及与 CD81 结合并能抑制或阻断疟原虫附着于 CD81 的配体，用于预防、抑制或治疗疟原虫感染的组合物和方法，以及靶向 CD81 上疟原虫结合位点的配体及其制造和使用方法。CD81 开放构象细胞外大环上的一系列配体结合位点已被确定。几个重要的位点位于通过突变研究确定为疟原虫结合位点的区域。识别这些位点的配体也已确定。将与靶蛋白上不同结构独特位点具有低度或中度亲和力的两种或三种配体连接在一起，可生成与 CD81 靶点具有极高亲和力的小分子配体共轭物。此外，还利用基于片段的药物设计方法设计了混合配体分子，以生成比母体化合物与蛋白质结合更紧密的配体类似物。鉴定和设计与 CD81 结合的化合物组，用于治疗受疟原虫感染的病人和与 CD81 有相互作用的病原体。通过与 CD81 结合，这些分子可以：1）阻止疟原虫附着和进入细胞（感染），特别是肝细胞；2）阻止或抑制疟原虫引起的炎症反应；3）阻止或抑制诱发与疟原虫感染有关的其他病症。
• Inhibitors of glucose kinases, along with methods of their formation and use
  申请人：University of South Carolina

  公开号：US10682359B2

  公开（公告）日：2020-06-16

  Compounds discovered through a high-throughput screen, along with methods of use of the compounds, are provided. The compounds can be used to strongly inhibit key drug targets found in protozoan parasites, e.g., the target Trypanosoma cruzi glucokinase. Compounds include derivatives of N-phenylbenzenesulfonamide, barbituric acid, (R)-3-(piperidin-2-yl)pyridine, 3-nitro-2-phenyl-2H-chromene, 6-amino-3-methyl-4-phenyl-1,4-dihydropryranole[2,3-c]pyrazole-5-carbonitrile, and gossypol (2,2′-Bis(formyl-1,6,7-trihydroxy-5-isopropyl-3-methylnaphthalene).

  本文提供了通过高通量筛选发现的化合物以及使用这些化合物的方法。这些化合物可用于强效抑制原生动物寄生虫中发现的关键药物靶标，例如靶标克氏锥虫葡萄糖激酶。化合物包括 N-苯基苯磺酰胺、巴比妥酸、(R)-3-(哌啶-2-基)吡啶、3-硝基-2-苯基-2H-色烯的衍生物、6-氨基-3-甲基-4-苯基-1,4-二氢吡喃烯并[2,3-c]吡唑-5-甲腈，以及棉酚（2,2′-双（甲酰基-1,6,7-三羟基-5-异丙基-3-甲基萘）。

表征谱图