1-(9-氮杂双环[4.2.1]壬-2-烯-2-基)乙酮 | 85514-42-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 类毒素
• 中文名称: 1-(9-氮杂双环[4.2.1]壬-2-烯-2-基)乙酮
• 英文名称: anatoxin-a
• 英文别名: Ethanone, 1-(9-azabicyclo(4.2.1)non-2-en-2-yl)-, (1R)-；1-(9-azabicyclo[4.2.1]non-2-en-2-yl)ethanone
• CAS: 85514-42-7
• 化学式: C₁₀H₁₅NO
• 分子量: 165.235
• InChiKey: SGNXVBOIDPPRJJ-UHFFFAOYSA-N

物化性质

• 颜色/状态：
  Oil
• 溶解度：
  In water, 7.2X10+4 mg/L at 25 °C (est)
• 蒸汽压力：
  5.8X10-3 mm Hg at 25 °C (est)
• 分解：
  When heated to decomposition it emits toxic fumes of nitrogen oxides.
• 解离常数：
  pKa = 9.4

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

颤藻PCC 6506等蓝藻产生的阿纳托克辛-a和同阿纳托克辛-a是强效的神经毒素。该菌株的基因组测序正在进行中，并且已经识别出了一个包含被称为ks2 t的序列的29 kb DNA片段，此前已经显示这个序列对产生阿纳托克辛-a和同阿纳托克辛-a的颤藻蓝藻具有特异性。对这29 kb片段的生物信息学分析揭示了一个基因簇，并对其进行了注释。从anaA到anaH的八个连续基因产物的功能为阿纳托克辛-a和同阿纳托克辛-a的生物合成提供了线索。脯氨酸首先被装载到酰基载体蛋白上，其五元环被氧化到吡咯啉氧化态。这个活化的环然后依次装载到三个聚酮合酶模块上，进行延长、还原、环化和甲基化。最后一步是硫酯的水解和随后的脱羧。使用标记前体由PCC 6506产生的同阿纳托克辛-a的GC-MS和NMR分析证实，脯氨酸很可能是这些聚酮合酶的起始物质。特定的PCR扩增显示，在产生阿纳托克辛-a和同阿纳托克辛-a的蓝藻基因组中，anaC、anaE、anaF和anaG基因总是存在，而在不产生毒株的基因组中则不存在。带有组氨酸标签的AnaC被纯化到均质，并显示能催化脯氨酸装载到之前通过使用枯草杆菌Sfp磷脂酰转移酶转化为其全酶形式的带有组氨酸标签的AnaD上。所有这些数据都提供了强有力的证据，证明了颤藻PCC 6506中负责产生阿纳托克辛-a和同阿纳托克辛-a的基因簇已经被识别。

Anatoxin-a and homoanatoxin-a are potent neurotoxins produced by cyanobacteria such as Oscillatoria PCC 6506. Sequencing of the genome of this strain is underway, and ... a 29 kb DNA fragment containing a sequence called ks2 t... previously shown to be specific to Oscillatoria cyanobacteria producing anatoxin-a and homoanatoxin-a /was identified/. Bioinformatic analysis of this 29 kb fragment revealed a cluster of genes, which were annotated. The function assigned to the products of eight contiguous genes, from anaA to anaH, provides a clue to the biosynthesis of anatoxin-a and homoanatoxin-a. Proline is first loaded on an acyl carrier protein and its five-membered cycle oxidized to the pyrroline oxidation state. This activated ring is then successively loaded on three polyketide synthase modules for elongation, reduction, cyclization, and methylation. The final step is the hydrolysis of the thioester with subsequent decarboxylation. GC-MS and NMR analyses of homoanatoxin-a produced by PCC 6506 using labeled precursors confirm that proline is very likely the starter of these polyketide synthases. ... Specific PCR amplifications ... showed that the anaC, anaE, anaF, and anaG genes are always present in the genome of cyanobacteria producing anatoxin-a and homoanatoxin-a and absent in nonproducing strains. Histidine-tagged AnaC was purified to homogeneity and showed to catalyze the loading of proline on purified histidine-tagged AnaD that had been previously transformed into its holo form using the Bacillus subtilis Sfp phosphopantetheinyl transferase. All of these data provide strong evidence that ... the gene cluster responsible for the production of anatoxin-a and homoanatoxin-a in Oscillatoria PCC 6506 /has been identified/.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：鱼腥藻毒素A是一种油。鱼腥藻毒素A是由几种淡水蓝藻产生的一种神经毒素，与家畜和野生动物的致命中毒有关。人体研究：一名青少年在充满有毒鱼腥藻的池塘中摔跤和潜水后，因暴露于蓝绿藻毒素而死亡。蓝藻细胞在粪便样本中被发现，毒素在浮渣样本中被测量到。这名青少年和他的朋友都出现了严重的呕吐、腹泻和腹痛。在受影响较严重的人身上，这种情况在暴露后48小时以休克和抽搐告终。涉嫌的毒素鱼腥藻毒素A是一种快速作用的神经毒素，但没有关于人类暴露的数据。虽然神经毒素可能会通过呼吸抑制和抽搐导致死亡，但不会预期它会导致胃肠炎。动物研究：鱼腥藻毒素A是由几种蓝藻属产生的一种强效神经毒素。报告了因鱼腥藻毒素A暴露导致的野生动物和家畜死亡，这是由神经肌肉接头处乙酰胆碱受体的抑制驱动的毒性反应。随后神经元的去极化导致肌肉细胞的过度刺激。在怀孕的第12至14天（器官形成后），每天一次或三次分别给仓鼠腹腔注射200或125微克/千克体重的鱼腥藻毒素A，在第15天处死母鼠。每天三次的治疗导致所有胎儿在10窝中的1窝出现胎儿畸形（脑积水），几乎所有窝的胎儿生长迟缓。每天一次的治疗导致生长迟缓。未观察到母体毒性。鱼腥藻毒素A在小鼠睾丸中引起了剂量依赖性的组织病理学变化，如精子管的变性、精原细胞系的细胞间分离、精原细胞在管腔中的脱落、Sertoli细胞的空泡化和精原细胞的丢失。对Salmonella typhimurium TA 1535/pSK1002菌株进行了遗传毒性测试，有和没有代谢转化。毒素浓度分别为0.25、0.5、1和2微克/毫升。没有代谢转化时，鱼腥藻毒素A的最高无效浓度为0.25微克/毫升。在代谢激活时未检测到效果。1990年和1991年，狗在饮用苏格兰因什湖沿岸含有底栖蓝藻水华的水后死亡。受影响动物的中毒症状和实验室生物测试中水华提取物的极高神经毒性表明是由于蓝藻神经毒素引起的急性中毒。神经毒性水华主要是由底栖Oscillatoria物种组成，这些物种也在中毒狗的胃内容物中被观察到。胃内容物在生物测试中也是神经毒性的，其症状与Oscillatoria水华相同。蓝藻生物碱神经毒素鱼腥藻毒素A在水华提取物和中毒狗胃内容物中被鉴定。生态毒性研究：1985年在加拿大阿尔伯塔省埃德蒙顿北部约150公里的一个湖中观察到了蝙蝠的大量死亡。超过1000只Myotis spp.和灰蝙蝠（Lasiurus cinereus）因饮用湖中的水而死于“藻类中毒”。蓝藻水华被怀疑与丹麦湖泊中鸟类的死亡有关，发生在1993年7月和1994年6月至7月。鱼腥藻毒素A是鱼类免疫细胞的凋亡诱导剂。蟾蜍胚胎（Bufo arenarum）在第17和第25阶段暴露于0.03-30.0毫克/升的鱼腥藻毒素A，持续10天。不良影响包括剂量依赖性的短暂中枢神经系统抑制、水肿和失衡。最值得注意的是，在两组高剂量下，暴露后6-13天出现了100%的死亡率。

IDENTIFICATION AND USE: Anatoxin A is an oil. Anatoxin A is a neurotoxin produced by several freshwater cyanobacteria and implicated in lethal poisonings of domesticated animals and wildlife. HUMAN STUDIES: Teenager who had been wrestling and diving in a pond with a heavy scum of toxic Anabaena flos-aquae died through exposure to blue-green algal toxin. The cyanobacterial cells were found in fecal samples, and toxin was measured in scum samples. The teenager and his friend both suffered severe vomiting, diarrhea, and abdominal pain. In the more severely affected individual, this ended in shock and seizure 48 hr after exposure. The toxin implicated, anatoxin A, is a fast-acting neurotoxin, but there are no data on human exposure. A neurotoxin would not be expected to cause the gastroenteritis, though it could cause death through respiratory inhibition and convulsions. ANIMAL STUDIES: Anatoxin A is a potent neurotoxin produced by several genera of cyanobacteria. Deaths of wild and domestic animals due to anatoxin-a exposure have been reported following a toxic response that is driven by the inhibition of the acetylcholine receptors at neuromuscular junctions. The consequent neuron depolarization results in an overstimulation of the muscle cells. Doses of 200 or 125 ug/kg bw anatoxin A were given i.p. to hamsters one or three times per day, respectively, at days 12 to 14 of pregnancy (after organogenesis), and the dams were sacrificed at day 15. The treatment given three times per day caused fetal malformation (hydrocephaly) in all fetuses in one of 10 litters, and stunted growth in almost all litters. Treatment given once per day resulted in stunted growth. No maternal toxicity was observed. Anatoxin A caused dose-dependent histopathological changes in the testes of mice such as degenerations in seminiferous tubules, intercellular disassociation of spermatogenetic cell lines, sloughing of germ cells into tubular lumen, vacuolization in Sertoli cells and loss of germ cells. Genotoxicity test was conducted on Salmonella typhimurium TA 1535/pSK1002 strain, with and without metabolic transformation. The toxin concentrations were 0.25, 0.5, 1 and 2 ug/mL. The highest inefficient concentration of anatoxin A without metabolic transformation was 0.25 ug/m. No effects were detected with metabolic activation. Dog deaths occurred in 1990 and 1991 after the animals drank water containing blooms of benthic cyanobacteria along the shoreline of Loch Insh, Scotland. Signs of poisoning in the affected animals and the high neurotoxicity of bloom extracts in laboratory bioassays indicated acute poisoning due to cyanobacterial neurotoxin(s). The neurotoxic blooms consisted largely of benthic Oscillatoria species which were also observed in the stomach contents of the poisoned dogs. Stomach contents were also neurotoxic in bioassays with the same signs of poisoning as the Oscillatoria blooms. The cyanobacterial alkaloid neurotoxin anatoxin A was identified in bloom extracts and poisoned dog stomach contents. ECOTOXICITY STUDIES: A die-off of bats was observed in a lake about 150 km north of Edmonton, Alberta, Canada, in 1985. Over 1000 Myotis spp. and hoary bats (Lasiurus cinereus) died of 'algal poisoning' caused by an alkaloid when they drank water from the lake. Cyanobacterial blooms were implicated in bird kills at lakes in Denmark in July 1993 and June-July 1994. Anatoxin A is an inducer of apoptosis in fish immune cells. Stages 17 and 25 toad embryos (Bufo arenarum) were exposed to 0.03-30.0 mg/L of anatoxin-a for 10 days. Adverse effects included a dose-dependent transient CNS depression, edema and loss of equilibrium. Most notable was the occurrence of 100% mortality at the high dose in both groups 6-13 days post-exposure.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

Anatoxin-a 是中枢神经系统中存在的神经元α4β2和α4尼古丁型乙酰胆碱受体的激动剂，同时也是存在于神经肌肉接头的α12βγδ肌肉型nAchRs的激动剂。Anatoxin-a对这些受体的亲和力大约是乙酰胆碱的20倍。Anatoxin-a在中枢神经系统中的效力远低于神经肌肉接头。在海马和脑干神经元中，激活nAchRs所需的Anatoxin-a浓度是在外周神经系统所需浓度的5到10倍。Anatoxin-a的结合是不可逆的，并且Anatoxin-a nAchR复合物不能被乙酰胆碱酯酶分解。因此，nAchR暂时被锁定在开放状态，一段时间后就会变得不敏感。在这种不敏感状态下，nAchRs不再允许阳离子通过，这最终导致神经肌肉传递的阻塞。

Anatoxin-a is an agonist of both neuronal α4β2 and α4 nicotinic acetylcholine receptors present in the CNS as well as the α12βγδ muscle-type nAchRs that are present at the neuromuscular junction. Anatoxin-a has an affinity for these receptors that is about 20 times greater than that of acetylcholine. Anatoxin-a also shows much less potency in the CNS than in neuromuscular junctions. In hippocampal and brain stem neurons, a 5 to 10 times greater concentration of anatoxin-a was necessary to activate nAchRs than what was required in the PNS. Anatoxin-a binding is irreversible, and the anatoxin-a nAchR complex cannot be broken down by acetylcholinesterase. Thus, the nAchR is temporarily locked open and after a period of time becomes desensitized. In this desensitized state the nAchRs no longer let cations pass through, which ultimately leads to a blockage of neuromuscular transmission.

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

• 相互作用

全球的水生栖息地中有大约2000种蓝藻（蓝绿藻）。它们能够在广泛的环境条件下生存，并且其中一些能够产生强大的毒素。毒素的产生与快速生长期（水华）有关，25%-70%的水华可能是有毒的。阿纳毒素-a是一种生物碱神经毒素，在尼古丁受体上是一种强效的神经肌肉阻断剂。食用受污染的水后，急性毒性表现为快速发作的瘫痪、震颤、抽搐和死亡。人类通过娱乐水上活动和饮食补充可能会接触到这种毒素，但主要是通过饮用水。目前的研究旨在检查子宫内暴露对出生后存活率、生长和神经发育的影响，评估体外胚胎毒性的潜力，并通过口腔途径探讨阿纳毒素-a与藻类毒素微囊藻毒素-LR之间的协同关系。还报告了关于两栖动物毒性的初步研究结果。怀孕小鼠在妊娠第8-12天或第13-17天通过腹腔注射接受125或200微克/千克的阿纳毒素-a。在6天内监测幼崽的存活率和体重。在200微克/千克的剂量下，在两个处理期间都观察到了母体毒性（活动能力下降）。在出生后第1天或第6天，对幼崽的存活率或体重没有显著的处理相关影响。妊娠第13-17天的幼崽在出生后第6天、第12天和第20天进行了标准的神经发育成熟指标评估（翻正反射、负地性趋向和悬挂抓握时间）。没有观察到显著的出生后神经毒性。在妊娠第8天的小鼠胚胎中，暴露于0.1-25微米阿纳毒素-a 26-28小时，评估体外发育毒性。在不存在显著胚胎畸形的条件下，从1.0微米浓度开始，就注意到了小鼠卵黄囊血管的变化。在通过灌胃接受0、500或1000微克/千克微囊藻毒素-LR的小鼠中，测试了藻类毒素的协同作用，大约50分钟后，通过同样的途径接受0、500、1000或2500微克/千克阿纳毒素-a。在任何剂量下都没有发生死亡，并且没有观察到明确的毒性迹象。将17期和25期的蟾蜍胚胎（Bufo arenarum）暴露于0.03-30.0毫克/升的阿纳毒素-a 10天。不良影响包括剂量依赖性的暂时昏迷、水肿和失去平衡。最值得注意的是，在两个组别中，高剂量下在暴露后6-13天发生了100%的死亡率。初始暴露与死亡之间的观察延迟对于阿纳毒素-a来说是非常不寻常的。

Some 2000 species of cyanobacteria (blue-green algae) occur globally in aquatic habitats. They are able to survive under a wide range of environmental conditions and some produce potent toxins. Toxin production is correlated with periods of rapid growth (blooms) and 25%-70% of blooms may be toxic. Anatoxin-a is an alkaloid neurotoxin that acts as a potent neuro-muscular blocking agent at the nicotinic receptor. Acute toxicity, following consumption of contaminated water, is characterized by rapid onset of paralysis, tremors, convulsions and death. Human exposures may occur from recreational water activities and dietary supplements, but are primarily through drinking water. The current studies were conducted to examine the effect of in utero exposure on postnatal viability, growth and neurodevelopment, to evaluate the potential of in vitro embryotoxicity, and to explore the synergistic relationship between anatoxin-a and the algal toxin microcystin-LR by the oral route. The results of preliminary studies on amphibian toxicity are also reported. Time-pregnant mice received 125 or 200 ug/kg anatoxin-a by intraperitoneal injection on gestation days (GD) 8-12 or 13-17. Pup viability and weight were monitored over a 6-day period. Maternal toxicity (decreased motor activity) was observed at 200 ug/kg in both treatment periods. There were no significant treatment-related effects on pup viability or weight on postnatal day (PND) 1 or 6. The GD 13-17 pups were evaluated on PND 6, 12 and 20 for standard markers of neurodevelopmental maturation (righting reflex, negative geotaxis and hanging grip time). No significant postnatal neurotoxicity was observed. In vitro developmental toxicity was evaluated in GD 8 mouse embryos exposed to 0.1-25 um anatoxin-a for 26-28 hr. Perturbations in mouse yolk sac vasculature were noted from the 1.0 um concentration in the absence of significant embryonic dysmorphology. Potential algal toxin synergism was tested in mice receiving either 0, 500 or 1,000 ug/kg microcystin-LR by gavage and approximately 50 min later receiving either 0, 500, 1,000 or 2,500 ug/kg anatoxin-a by the same route. No deaths occurred at any dose and no definitive signs of intoxication were observed. Stages 17 and 25 toad embryos (Bufo arenarum) were exposed to 0.03-30.0 mg/L of anatoxin-a for 10 days. Adverse effects included a dose-dependent transient narcosis, edema and loss of equilibrium. Most notable was the occurrence of 100% mortality at the high dose in both groups 6-13 days post-exposure. The observed delay between initial exposure and death is highly unusual for anatoxin-a.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

兽医：对于类毒素-a没有特定的解毒剂。由于临床体征的迅速出现，催吐不太可能有用。尽管没有研究评估特定去污程序的疗效，但已推荐使用活性炭。此外，人工呼吸可能在一般支持性护理中有所帮助。控制癫痫的具体措施包括使用苯二氮卓类药物、苯巴比妥或戊巴比妥。如果使用这些药物，它们可能会导致中枢神经系统（CNS）和呼吸抑制，因此需要对动物进行仔细的监测。在任何发生癫痫的动物中，控制体温是症状护理的重要部分。

VET: There is no specific antidote for anatoxin-a. Because of the rapid onset of clinical signs, emesis is not likely to be useful. Although there are no studies that evaluate the efficacy of specific decontamination procedures, administration of activated charcoal has been recommended. In addition, artificial respiration may be of benefit along with general supportive care. Specific measures to control seizures include benzodiazepines, phenobarbital or pentobarbital. If given, they may cause central nervous system (CNS) and respiratory depression and careful monitoring of the animal is necessary. In any seizuring animal, control of body temperature is an important part of the symptomatic care.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  1-(9-氮杂双环[4.2.1]壬-2-烯-2-基)乙酮 在 盐酸 作用下， 以 氯仿 、 乙酸乙酯 为溶剂， 生成 (-)-变性毒素-A 富马酸酯
  参考文献：
  名称：

  Synthesis of anatoxin-a: very fast death factor

  摘要：

  DOI：

  10.1021/ja00337a059
• 作为产物：
  描述：

  (2R)-but-3-enyl-(5R)-prop-1-ynylpyrrolidine-1-carboxylic acid 1-benzyl ester 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) sodium periodate 、 四氧化锇 、 碘代三甲硅烷 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙腈 为溶剂， 生成 1-(9-氮杂双环[4.2.1]壬-2-烯-2-基)乙酮
  参考文献：
  名称：

  Application of Intramolecular Enyne Metathesis to the Synthesis of Aza[4.2.1]bicyclics:  Enantiospecific Total Synthesis of (+)-Anatoxin-a

  摘要：

  A concise synthesis of the potent nAChR agonist (+)-anatoxin-a (1) has been completed in a series of only nine chemical operations and 27% overall yield from commercially available D-methyl pyroglutamate (4). The synthesis features a novel procedure for the diastereoselective preparation of cis-2,5-disubstituted pyrrolidines leading to 10, which underwent an intramolecular enyne metathesis to afford a bridged azabicyclic intermediate that was transformed into 1.

  DOI：

  10.1021/ol049631e

文献信息

• USE OF ARYL CARBAMATES IN AGRICULTURE AND OTHER PLANT-RELATED AREAS
  申请人：North Carolina State University

  公开号：US20130172187A1

  公开（公告）日：2013-07-04

  Disclosure is provided for methods of preventing, removing or inhibiting microbial biofilm formation or microbial infection in a plant or plant part thereof, including applying thereto a treatment effective amount of an aryl carbamate as described herein, or an agriculturally acceptable salt thereof. Methods of enhancing a microbicide (e.g., including a copper, antibiotic, bacteriophage, etc.) and/or plant defense activator are also provided, including applying an active compound as described herein. Compositions comprising an aryl carbamate compound as described herein in an agriculturally acceptable carrier are also provided, and in some embodiments the compositions further include a microbicide (e.g., including copper, antibiotic, bacteriophage, etc.) and/or a plant defense activator.

  本公开提供了一种防止、去除或抑制植物或其部分中微生物生物膜形成或微生物感染的方法，包括向其施加本文所述的芳基氨基甲酸酯或其农业可接受的盐的治疗有效量。还提供了增强微生物杀灭剂（例如，包括铜、抗生素、噬菌体等）和/或植物防御激活剂的方法，包括施加本文所述的活性化合物。还提供了包含本文所述的芳基氨基甲酸酯化合物的组合物，其在农业上可接受的载体中，并且在某些实施例中，这些组合物进一步包括微生物杀灭剂（例如，包括铜、抗生素、噬菌体等）和/或植物防御激活剂。
• PREPARATION OF BIOCONJUGATES AND ANTIBODIES FOR THE IMMUNODETECTION OF ANATOXIN-A
  申请人：CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS

  公开号：US20190265233A1

  公开（公告）日：2019-08-29

  The present invention relates to bioconjugates and labeled derivatives of anatoxin-a, at different positions of the molecule, suitable for producing antibodies with high affinity and specificity for anatoxin-a. At the same time, the present invention also relates to the use of bioconjugates of anatoxin-a and labeled derivatives of anatoxin-a as assay antigens. Moreover, the present invention also relates to methods for analyzing, concentrating and extracting anatoxin-a using the antibodies obtained, sometimes together with assay antigens which are bioconjugates or labeled derivatives. This invention also provides a kit for analyzing anatoxin-a which comprises antibodies against this cyanotoxin sometimes together with assay antigens which are bioconjugates or labeled derivatives of anatoxin-a.

  本发明涉及生物共轭物和标记衍生物的解剖素以及不同分子位置的阿托西辛-a，适用于产生对阿托西辛-a具有高亲和力和特异性的抗体。同时，本发明还涉及使用阿托西辛-a的生物共轭物和标记衍生物作为测定抗原。此外，本发明还涉及利用所得抗体对阿托西辛-a进行分析、浓缩和提取的方法，有时还与生物共轭物或标记衍生物作为测定抗原一起使用。本发明还提供了一种用于分析阿托西辛-a的试剂盒，其中包括针对这种蓝藻毒素的抗体，有时还与生物共轭物或标记衍生物的测定抗原一起使用。
• Azabicyclo and azacyclo oxime and amine cholinergic agents and methods
  申请人：Warner-Lambert Company

  公开号：US05482938A1

  公开（公告）日：1996-01-09

  Pharmaceutically useful nitrogen containing cyclic oxime and amine substituted compounds are disclosed which are azabicyclo[2.2.2]oximes, azabicyclo[2.2.2]-amines, azabicyclo[3.2.1]oximes and amine containing heterocyclic oximes wherein the heterocyclic ring contains from 3 to 7 carbon atoms.

  本文披露了一些具有药用价值的氮杂环氧酮和胺取代化合物，包括：含有氮杂环[2.2.2]氧酮、含有氮杂环[2.2.2]胺、含有氮杂环[3.2.1]氧酮和含有胺基的杂环氧酮，其中杂环环中含有3至7个碳原子。
• METHODS AND COMPOSITIONS FOR IDENTIFYING, PRODUCING AND USING PLANT-DERIVED PRODUCTS FOR MODULATING CELL FUNCTION AND AGING
  申请人：McDaniel David H.

  公开号：US20110159121A1

  公开（公告）日：2011-06-30

  Provided herein are methods of culturing cells in vitro in order to exploit the biochemical production ability of the cells to make metabolites that are evaluated and harvested for their biological effects. Also provided are systems for evaluating extracts from such cultured cells to characterize their biological activity(s), particularly with regard to impact on health, wellbeing, longevity, DNA maintenance, mitochondrial health and/or biogenesis, and so forth. Biologically active extracts, components thereof, and compositions (such as cosmetic or pharmaceutical preparations) made comprising such, are also provided.

  本文提供了在体外培养细胞的方法，以利用细胞的生化生产能力来制造代谢产物，这些代谢产物被评估和收获其生物效应。还提供了用于评估这些培养细胞提取物的系统，以表征其生物活性，特别是对健康、幸福、长寿、DNA维护、线粒体健康和/或生成等方面的影响。还提供了具有生物活性的提取物、其组分以及制成的组合物（如化妆品或制药制剂）。
• Azabicyclo and azacyclo oxime and amine cholinergic agents and pharmaceutically acceptable salts thereof
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0445731A1

  公开（公告）日：1991-09-11

  Pharmaceutically useful nitrogen containing cyclic oxime and amine substituted compounds of the formula which are azabicyclo[2.2.1]oximes, azabizyclo[2.2.2]oximes, azabicyclo[2.2.1]amines, azabicyclo[2.2.2]amines, azabicyclo[3.2.1]oximes and amine containing heterocyclic oximes wherein the heterocyclic ring contains from 3 to 7 carbon atoms. These compounds are useful as analgesics and for the treatment of cognitive decline in a patient.

  药用含氮环肟和胺取代的式化合物 其中包括氮杂双环[2.2.1]肟、氮杂双环[2.2.2]肟、氮杂双环[2.2.1]胺、氮杂双环[2.2.2]胺、氮杂双环[3.2.1]肟和含胺杂环肟，其中杂环含有 3 至 7 个碳原子。这些化合物可用作镇痛剂和治疗患者认知能力下降。