(+/-)-尼古丁 | 22083-74-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: (+/-)-尼古丁
• 中文别名: 烟碱D7；1-甲基-2-(3-吡啶基)吡咯烷,1-METHY-2-(3-PYRIDYL)PYRROLIDINE；尼古丁-D7消旋；尼可丁；菸碱(尼古丁)；3-[1-甲基-2-吡咯烷基]吡啶
• 英文名称: 3-(1-methyl-pyrrolidin-2-yl)-pyridine
• 英文别名: nicotine；(R,S)-nicotine；3-(1-Methylpyrrolidin-2-yl)pyridine
• CAS: 22083-74-5
• 化学式: C₁₀H₁₄N₂
• mdl: MFCD00065370
• 分子量: 162.235
• InChiKey: SNICXCGAKADSCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 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：
  16.1
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

代谢

尼古丁已知的人类代谢物包括尼古丁N-葡萄糖苷酸。

Nicotine has known human metabolites that include Nicotine N-glucuronide.

来源:NORMAN Suspect List Exchange

代谢

当尼古丁进入人体时，它会迅速通过血液循环分布，并能够穿越血脑屏障。平均而言，吸入时大约需要七秒钟物质才能到达大脑。尼古丁在体内的半衰期大约是两小时。尼古丁在肝脏中被细胞色素P450酶（主要是CYP2A6，还有CYP2B6）代谢。一个主要的代谢物是可替宁。其他主要的代谢物包括尼古丁N'-氧化物、降烟碱、尼古丁异甲铵离子、2-羟基尼古丁和尼古丁葡萄糖醛酸苷。(L327) 消除途径：吸收的大约10%的尼古丁以原形通过尿液排出。 半衰期：可替宁的半衰期为15-20小时，而尼古丁的半衰期为1-3小时。

As nicotine enters the body, it is distributed quickly through the bloodstream and can cross the blood-brain barrier. On average it takes about seven seconds for the substance to reach the brain when inhaled. The half life of nicotine in the body is around two hours. Nicotine is metabolized in the liver by cytochrome P450 enzymes (mostly CYP2A6, and also by CYP2B6). A major metabolite is cotinine. Other primary metabolites include nicotine N'-oxide, nornicotine, nicotine isomethonium ion, 2-hydroxynicotine and nicotine glucuronide. (L327) Route of Elimination: About 10% of the nicotine absorbed is excreted unchanged in the urine. Half Life: Cotinine has a half life of 15-20 hours, while nicotine has a half life of 1-3 hours

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

尼古丁是一种兴奋剂药物，它在尼古丁乙酰胆碱受体上充当激动剂。这些是由五个同聚体或异聚体亚单位组成的离子通道受体。在大脑中，尼古丁结合到皮质边缘路径中的多巴胺能神经元的尼古丁乙酰胆碱受体上。这导致通道打开，允许多种阳离子包括钠、钙和钾的导电性。这导致去极化，激活电压门控钙通道，允许更多的钙进入轴突末端。钙刺激囊泡向质膜运输和将多巴胺释放到突触中。多巴胺与其受体的结合负责尼古丁的愉悦和成瘾性质。 尼古丁还结合到肾上腺髓质中的嗜铬细胞上的尼古丁乙酰胆碱受体。结合打开离子通道，允许钠流入，导致细胞去极化，激活电压门控钙通道。钙触发从细胞内囊泡释放肾上腺素进入血液，这导致血管收缩、血压升高、心率增加和血糖升高。

Nicotine is a stimulant drug that acts as an agonist at nicotinic acetylcholine receptors. These are ionotropic receptors composed up of five homomeric or heteromeric subunits. In the brain, nicotine binds to nicotinic acetylcholine receptors on dopaminergic neurons in the cortico-limbic pathways. This causes the channel to open and allow conductance of multiple cations including sodium, calcium, and potassium. This leads to depolarization, which activates voltage-gated calcium channels and allows more calcium to enter the axon terminal. Calcium stimulates vesicle trafficking towards the plasma membrane and the release of dopamine into the synapse. Dopamine binding to its receptors is responsible the euphoric and addictive properties of nicotine. Nicotine also binds to nicotinic acetylcholine receptors on the chromaffin cells in the adrenal medulla. Binding opens the ion channel allowing influx of sodium, causing depolarization of the cell, which activates voltage-gated calcium channels. Calcium triggers the release of epinephrine from intracellular vesicles into the bloodstream, which causes vasoconstriction, increased blood pressure, increased heart rate, and increased blood sugar.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

尼古丁具有改变情绪的作用，可能包括放松、敏锐、平静和警觉。根据剂量不同，它可能起到兴奋剂或镇静剂/止痛剂的作用。

Nicotine has mood-altering effects that may include relaxation, sharpness, calmness, and alertness. It may act as a stimulant or sedative/pain killer, depending on the dosage. (L327)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概述：此记录中的信息仅指尼古丁作为戒烟替代品的使用。使用21毫克的透皮贴片时，尼古丁进入母乳的量相当于每天吸烟17支香烟。7毫克和14毫克较低剂量的贴片为哺乳婴儿提供的尼古丁量按比例降低。尚未有关于哺乳期母亲使用尼古丁喷雾或尼古丁口香糖的研究报告。使用尼古丁喷雾后，母体血浆尼古丁浓度约为吸烟者的三分之一，因此乳汁中的浓度可能按比例降低。使用尼古丁口香糖后，母体尼古丁血浆浓度因咀嚼的力度和每天咀嚼的数量而有所不同，但可能与吸烟香烟后达到的浓度相似。一个来源建议使用作用时间较短的制剂而不是贴片。 有些人主张在吸烟的母亲中使用尼古丁替代产品，以减少母乳喂养婴儿吸入烟雾和母体香烟烟雾中毒素的风险。然而，其他人指出，基于动物数据，尼古丁可能增加婴儿猝死综合症的风险，并可能干扰婴儿正常肺部的发育。这些作者建议哺乳期母亲不要使用任何形式的尼古丁。尚未有研究解决这些问题。在哺乳期间，可能更愿意使用另一种戒烟产品。 ◉ 对哺乳婴儿的影响：母亲吸烟是婴儿猝死综合症（SIDS）的主要危险因素。认为尼古丁是致病因素，因为它减少了颈动脉体的多巴胺含量，并减少了婴儿在缺氧发作期间自我复苏的能力。 吸烟者母乳中的尼古丁似乎也会降低男性哺乳婴儿的心率变异性。 在一项研究中，5位使用21毫克尼古丁贴片戒烟的母亲所生的婴儿，其平均丹佛发展年龄相当于他们的实际年龄。 ◉ 对泌乳和母乳的影响：吸烟会减少乳汁产量。这种效应可能是由尼古丁引起的，因为尼古丁降低了血清催乳素，尽管吸烟的其他因素也可能发挥作用。 在一项研究中，15位使用尼古丁贴片的哺乳期母亲在几周内剂量从21毫克降至14毫克再到7毫克，她们的平均产奶量比文献平均价值低17%，根据婴儿的奶摄入量判断。然而，该研究并未直接比较吸烟者与非吸烟者的乳汁产量。在这项研究中，母亲使用尼古丁贴片期间婴儿的奶摄入量与吸烟期间相似。

◉ Summary of Use during Lactation:Information in this record refers only to the use of nicotine as a replacement product for smoking cessation. With a 21 mg transdermal patch, nicotine passes into breastmilk in amounts equivalent to smoking 17 cigarettes daily. Lower patch strengths of 7 and 14 mg provide proportionately lower amounts of nicotine to the breastfed infant. No studies on nicotine spray or nicotine gum use in nursing mothers have been reported. Maternal plasma nicotine concentrations after using the nicotine spray are about one-third those of smokers, so milk concentrations are probably proportionately less. Maternal nicotine plasma concentrations after using nicotine gum are variable depending on the vigor of chewing and number of pieces chewed daily, but can be similar to those attained after smoking cigarettes. One source recommends the shorter acting agents over the patches. Some have advocated use of nicotine replacement products in smoking mothers to reduce the risk to breastfed infants of inhaled smoke and toxins in maternal cigarette smoke. However, others point out that based on animal data, nicotine may increase the risk of sudden infant death syndrome and might interfere with normal infant lung development. These authors recommend against using any form of nicotine in nursing mothers. No studies have been performed to resolve these issues. An alternate smoking cessation product may be preferred during nursing. ◉ Effects in Breastfed Infants:Maternal smoking is a major risk factor for sudden infant death syndrome (SIDS). Nicotine is thought to be the causative factor by reducing the dopamine content of the carotid bodies and reducing the infant's ability to autoresuscitate during hypoxic episodes. Nicotine in the breastmilk of smokers also appears to reduce the heart rate variability in male breastfed infants. In a study of the infants of 5 mothers who were using 21 mg nicotine patches for smoking cessation, the infants' average Denver Developmental age was equivalent to their chronological age. ◉ Effects on Lactation and Breastmilk:Cigarette smoking reduces milk yield. This effect may be caused by nicotine which lowers serum prolactin, although other factors associated with smoking may also play a role. In a study of 15 nursing mothers who were using nicotine patches in decreasing doses from 21 mg to 14 mg to 7 mg over several weeks, their average milk production was 17% lower than average literature values as judged by infant milk intake. The study did not directly compare the milk production of smokers to nonsmokers, however. In this study, infant milk intake during maternal use of the nicotine patch was similar to that during smoking.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 暴露途径

口服（L327）；吸入（L327） 尼古丁通过口腔黏膜的吸收相对较慢，并且与吸烟时看到的尼古丁动脉血浆浓度的高而快速上升随后下降不同，吸入器无法达到这种效果。大约10%被吸收的尼古丁以不变的形式从尿液中排出。

Oral (L327) ; Inhalation (L327) Absorption of nicotine through the buccal mucosa is relatively slow and the high and rapid rise followed by the decline in nicotine arterial plasma concentrations seen with cigarette smoking are not achieved with the inhaler. About 10% of absorbed nicotine is excreted unchanged in urine.

来源:Toxin and Toxin Target Database (T3DB)

安全信息

• 储存条件：
  | 冰箱 |

制备方法与用途

(+/-)-尼古丁的制备 方法一

将烟叶与石灰石一同进行蒸馏，然后用乙醚萃取出尼古丁。

反应信息

• 作为反应物：
  描述：

  (+/-)-尼古丁 在 ammonia borane 、 6-hydroxy-D-nicotine oxidase 作用下， 反应 16.0h， 以93%的产率得到烟碱
  参考文献：
  名称：

  具有宽底物特异性和高对映选择性的R选择性胺氧化酶的开发

  摘要：

  胺氧化酶是用于合成对映体纯的1°，2°和3°手性胺的有用生物催化剂。先前报道的此类酶（例如，来自黑曲霉的MAO-N ）已显示出高度的S选择性。在此，我们报道了基于6-羟基-D-烟碱氧化酶（6-HDNO）的对映体互补R-选择性胺氧化酶的开发，该酶具有扩大的底物范围和高对映选择性。工程化的6-HDNO酶已应用于一系列外消旋胺的制备脱硝反应，以产生具有S构型的产物，例如高ee的（S）-烟碱。

  DOI：

  10.1002/cctc.201301008
• 作为产物：
  描述：

  烟碱 在 15-冠醚-5 、 sodium t-butanolate 作用下， 反应 2.0h， 以94.7%的产率得到(+/-)-尼古丁
  参考文献：
  名称：

  一种吡啶衍生物的消旋方法及应用

  摘要：

  本发明属于药物领域，尤其涉及一种吡啶衍生物的消旋方法及应用，该方法包括如下步骤：如下式I所示的吡啶衍生物在碱和相转移催化剂作用下进行消旋反应，经后处理得到吡啶衍生物消旋体；式I如下所示：；式中，n选自‑3、‑2、‑1、0、1、2或3；R表征氢或C1‑C7含碳基团；所述碱选自氢氧化钾、氢氧化钠、碱金属醇盐中的至少一种；所述相转移催化剂选自18‑冠醚‑6、18‑冠醚‑6衍生物、15‑冠醚‑5或15‑冠醚‑5衍生物；反应温度为20℃‑200℃。本发明提供的吡啶衍生物的消旋方法条件温和，消旋速度快，副反应少，收率高，成本低，实用价值高，适用于大规模工业化生产应用。

  公开号：

  CN112174763A
• 作为试剂：
  描述：

  异麦芽酮糖醇 、 薄荷脑 、 disodium;carbonate 、 、 2,3-Dihydroxybutanedioic acid;3-(1-methylpyrrolidin-2-yl)pyridine;dihydrate 在 (+/-)-尼古丁 作用下， 以 水 为溶剂， 生成 (+/-)-尼古丁
  参考文献：
  名称：

  Nicotine-containing oral dosage form

  摘要：

  本发明涉及一种玻璃基质固体口服剂型，用于经口黏膜给药尼古丁活性物质。

  公开号：

  US20040101543A1

文献信息

• [EN] BENZAMIDE OR BENZAMINE COMPOUNDS USEFUL AS ANTICANCER AGENTS FOR THE TREATMENT OF HUMAN CANCERS<br/>[FR] COMPOSÉS BENZAMIDE OU BENZAMINE À UTILISER EN TANT QU'ANTICANCÉREUX POUR LE TRAITEMENT DE CANCERS HUMAINS
  申请人：UNIV TEXAS

  公开号：WO2017007634A1

  公开（公告）日：2017-01-12

  The described invention provides small molecule anti-cancer compounds for treating tumors that respond to cholesterol biosynthesis inhibition. The compounds selectively inhibit the cholesterol biosynthetic pathway in tumor-derived cancer cells, but do not affect normally dividing cells.

  所描述的发明提供了用于治疗对胆固醇生物合成抑制作出反应的肿瘤的小分子抗癌化合物。这些化合物选择性地抑制肿瘤来源的癌细胞中的胆固醇生物合成途径，但不影响正常分裂的细胞。
• BENZOTHIOPHENE INHIBITORS OF RHO KINASE
  申请人：Kahraman Mehmet

  公开号：US20080021026A1

  公开（公告）日：2008-01-24

  The present invention relates to compounds and methods which may be useful as inhibitors of Rho kinase for the treatment or prevention of disease.

  本发明涉及化合物和方法，这些化合物和方法可能作为Rho激酶的抑制剂在治疗或预防疾病方面有用。
• [EN] AZA PYRIDONE ANALOGS USEFUL AS MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS<br/>[FR] ANALOGUES D'AZAPYRIDONE UTILES COMME ANTAGONISTES DU RÉCEPTEUR 1 DE L'HORMONE CONCENTRANT LA MÉLANINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2010104818A1

  公开（公告）日：2010-09-16

  MCHR1 antagonists are provided having the following Formula (I): A1 and A2 are independently C or N; E is C or N; Q1, Q2, and Q3 are independently C or N provided that at least one of Q1, Q2, and Q3 is N but not more than one of Q1, Q2, and Q3 is N; D1 is a bond, -CR8R9 X-, -XCR8R9-, -CHR8CHR9-, -CR10=CR10'-, -C≡C-, or 1,2-cyclopropyl; X is O, S or NR11; R1, R2, and R3 are independently selected from the group consisting of hydrogen, halogen, lower alkyl, lower cycloalkyl, -CF3, -OCF3, -OR12 and -SR12; G is O, S or -NR15; D2 is lower alkyl, lower cycloalkyl, lower alkylcycloalkyl, lower cycloalkylalkyl, lower cycloalkoxyalkyl or lower alkylcycloalkoxy or when G is NR15, G and D2 together may optionally form an azetidine, pyrrolidine or piperidine ring; Z1 and Z2 are independently hydrogen, lower alkyl, lower cycloalkyl, lower alkoxy, lower cycloalkoxy, halo, -CF3, -OCONR14R14', -CN, -CONR14R14', -SOR12, -SO2R12, -NR14COR14', -NR14CO2R14', -CO2R12, NR14SO2R12 or COR12; R5, R6, and R7 are independently selected from the group consisting of hydrogen lower alkyl, lower cycloalkyl, -CF3, -SR12, lower alkoxy, lower cycloalkoxy, -CN, -CONR14R14', SOR12, SO2R12, NR14COR14', NR14CO2R12, CO2R12, NR14SO2R12 and -COR12; R8, R9, R10, R10', R11 are independently hydrogen or lower alkyl; R12 is lower alkyl or lower cycloalkyl; R14 and R14' are independently H, lower alkyl, lower cycloalkyl or R14 and R14' together with the N to which they are attached form a ring having 4 to 7 atoms; and R15 is independently selected from the group consisting of hydrogen and lower alkyl. Such compounds are useful for the treatment of MCHR1 mediated diseases, such as obesity, diabetes, IBD, depression, and anxiety.

  MCHR1拮抗剂具有以下化学式（I）：A1和A2独立地为C或N；E为C或N；Q1、Q2和Q3独立地为C或N，但至少其中一个为N，但不超过一个为N；D1为键，-CR8R9 X-，-XCR8R9-，-CHR8CHR9-，-CR10=CR10'-，-C≡C-，或1,2-环丙基；X为O、S或NR11；R1、R2和R3独立地从氢、卤素、低烷基、低环烷基、-CF3、-OCF3、-OR12和-SR12组成的群体中选择；G为O、S或-NR15；D2为低烷基、低环烷基、低烷基环烷基、低环烷基烷基、低环烷氧基烷基或低烷基环烷氧基，或当G为NR15时，G和D2一起可以选择形成氮杂环丙烷、吡咯烷或哌啶环；Z1和Z2独立地为氢、低烷基、低环烷基、低烷氧基、低环烷氧基、卤素、-CF3、-OCONR14R14'、-CN、-CONR14R14'、-SOR12、-SO2R12、-NR14COR14'、-NR14CO2R14'、-CO2R12、NR14SO2R12或COR12；R5、R6和R7独立地从氢、低烷基、低环烷基、-CF3、-SR12、低烷氧基、低环烷氧基、-CN、-CONR14R14'、SOR12、SO2R12、NR14COR14'、NR14CO2R12、CO2R12、NR14SO2R12和-COR12组成的群体中选择；R8、R9、R10、R10'、R11独立地为氢或低烷基；R12为低烷基或低环烷基；R14和R14'独立地为H、低烷基、低环烷基或R14和R14'与其连接的N一起形成具有4至7个原子的环；R15独立地从氢和低烷基组成的群体中选择。这些化合物对于治疗MCHR1介导的疾病，如肥胖症、糖尿病、炎症性肠病、抑郁症和焦虑症非常有用。
• [EN] QUINUCLIDINE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS<br/>[FR] COMPOSÉS QUINUCLIDINE EN TANT QUE LIGANDS DU RÉCEPTEUR NICOTINIQUE ALPHA-7 DE L'ACÉTYLCHOLINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2016073407A1

  公开（公告）日：2016-05-12

  There are disclosed a series of quinuclidines having the Formula (I). which bind to the nicotinic α7 receptor and may be useful for the treatment of disorders of the central nervous system.

  揭示了一系列具有化学式（I）的喹诺啉类化合物，它们与尼古丁型α7受体结合，可能对中枢神经系统疾病的治疗有用。
• [EN] BICYCLYL-SUBSTITUTED ISOTHIAZOLINE COMPOUNDS<br/>[FR] COMPOSÉS ISOTHIAZOLINE SUBSTITUÉS PAR UN BICYCLYLE
  申请人：BASF SE

  公开号：WO2014206910A1

  公开（公告）日：2014-12-31

  The present invention relates to bicyclyl-substituted isothiazoline compounds of formula (I) wherein the variables are as defined in the claims and description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.

  本发明涉及公式（I）中变量如索权和说明中所定义的自行车基取代异噻唑啉化合物。这些化合物对抗或控制无脊椎动物害虫，特别是节肢动物害虫和线虫方面具有用途。该发明还涉及一种通过使用这些化合物来控制无脊椎动物害虫的方法，以及包含所述化合物的植物繁殖材料、农业和兽医组合物。

表征谱图