欧前胡素 | 482-44-0

• 物质功能分类: 生物化工 - 中草药成分
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 中文名称: 欧前胡素
• 中文别名: 前胡素
• 英文名称: imperatorin
• 英文别名: 9-(3-methylbut-2-enyloxy)-7H-furo[3,2-g]chromen-7-one；marmelosin；8-isopentenyloxypsoralen；9-((3-methylbut-2-en-1-yl)oxy)-7H-furo[3,2-g]chromen-7-one；imperatonin；isoimperatorin；ammidin；Pentosalen；9-(3-methylbut-2-enoxy)furo[3,2-g]chromen-7-one
• CAS: 482-44-0
• 化学式: C₁₆H₁₄O₄
• mdl: MFCD00016881
• 分子量: 270.285
• InChiKey: OLOOJGVNMBJLLR-UHFFFAOYSA-N

物化性质

• 熔点：
  98-100°C
• 沸点：
  333.4°C (rough estimate)
• 密度：
  1.1311 (rough estimate)
• 溶解度：
  二甲基亚砜：≥5mg/mL
• 最大波长(λmax)：
  301nm(MeOH)(lit.)
• LogP：
  2.983 (est)
• 物理描述：
  Solid
• 颜色/状态：
  Prisms from ether, long needles from hot water
• 稳定性/保质期：

  Stable under recommended storage conditions.

• 分解：
  Hazardous decomposition products formed under fire conditions - Carbon oxides.
• 保留指数：
  2356

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.187
• 拓扑面积：
  48.7
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

Impatorin（IMP）是许多草药药物的主要成分，具有抗骨质疏松活性。目前的研究工作旨在研究IMP的生物转化过程，并评估转化代谢物的抗骨质疏松活性。在筛选的18株丝状真菌中，Penicillium janthinellum AS 3.510显示出将IMP代谢为新衍生物的良好能力。分离并纯化了10种转化产物，并基于光谱数据准确鉴定了它们的结构。8种代谢物（2-8和10）是新的，之前未见报道。主要的生物转化反应涉及前氧基侧链的羟基化和呋喃香豆素骨架的 lactone 环开反应。此外，使用MC3T3-E1细胞评估了所有产物（1-10）的抗骨质疏松活性。结果显示，产物5和8在增加MC3T3-E1细胞生长方面具有最佳的生物活性。这些产物可用于未来治疗骨质疏松症的治疗方案。

Imperatorin (IMP) is a major constituent of many herbal medicines and possesses anti-osteoporosis activity. The present research work aimed to study the biotransformation processes of IMP and evaluated the anti-osteoporosis activity of the transformed metabolites. Among 18 strains of filamentous fungi screened, Penicillium janthinellum AS 3.510 exhibited good capability to metabolize IMP to the new derivatives. Ten transformed products were isolated and purified, and their structures were identified accurately based on spectroscopic data. Eight metabolites (2-8 and 10) were novel and previously unreported. The major biotransformation reactions involved hydroxylation of the prenyloxy side-chain and the lactone ring-opening reaction of furocoumarin skeleton. In addition, anti-osteoporosis activities of all products (1-10) were evaluated using MC3T3-E1 cells. The results showed that products 5 and 8 had the best bioactivities in increasing MC3T3-E1 cell growth. These products could be used in future therapeutic regimens for treating osteoporosis.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在本研究中，开发了一种简单灵敏的气相色谱-质谱方法，用于研究氧化欧前胡素在大鼠体内的生物利用度、蛋白结合以及代谢。结果显示，氧化欧前胡素在大鼠静脉注射和口服给药后的药代动力学呈现线性特征。氧化欧前胡素的绝对生物利用度分别计算为约3.85%、约33.51%和约34.76%，对应的给药剂量为6.25、12.5和25 mg/kg。氧化欧前胡素低生物利用度可能归因于吸收不良或广泛代谢。研究了氧化欧前胡素在大鼠肝微粒体体外形成的I相代谢物，并分离并鉴定出两种代谢物为花椒毒素和川楝素。口服给药氧化欧前胡素后，在大鼠血浆中检测到一种代谢物（川楝素），在大鼠尿液中检测到两种潜在代谢物（花椒毒素和川楝素）。然而，在大鼠粪便和胆汁中没有检测到潜在代谢物。结果表明，氧化欧前胡素的代谢物通过肾脏排出，川楝素与活性成分有关。去甲基化和氧化是主要的代谢途径。体外血浆蛋白结合实验表明，氧化欧前胡素在1.0和50.0微克/毫升的加标大鼠血浆浓度下的蛋白结合率分别为90.1%和92.6%，表明氧化欧前胡素在细胞内外空间的分布缓慢。

In this study, a simple and sensitive gas chromatography-mass spectrometry method was developed for the study of bioavailability and protein binding and the metabolism of imperatorin in rat. The results showed that the pharmacokinetics of imperatorin after intravenous and oral administration in rats exhibited linear characteristics. The absolute bioavailability of imperatorin was calculated as approximately 3.85, approximately 33.51 and approximately 34.76% for 6.25, 12.5 and 25 mg/kg, respectively. The low bioavailability of imperatorin may be attributed to the poor absorption or extensive metabolism. The phase I metabolites of imperatorin formed in vitro by rat liver microsomes were studied, and two metabolites were isolated and identified as xanthotoxol and heraclenin. Following oral administration of imperatorin, one metabolite (heraclenin) was detected in rat plasma, and two potential metabolites (xanthotoxol and heraclenin) were detected in rat urine. However, none of potential metabolites was detected in rat feces and bile. The results showed that the metabolites of imperatorin were excreted by kidney, and heraclenin was associated with an active component. Demethylation and oxygenization were the main metabolic pathways. In vitro plasma protein binding of imperatorin was 90.1 and 92.6% for the spiked rat plasma concentrations of 1.0 and 50.0 ug/mL, respectively, indicating that imperatorin showed slow distribution into the intra- and extracellular space.

来源:Hazardous Substances Data Bank (HSDB)

代谢

对氧磷酶（PON1）是有机磷代谢的关键酶。PON1可以通过水解使一些有机磷失活。PON1水解多种有机磷杀虫剂以及神经毒剂（如梭曼、沙林和VX）的活性代谢物。PON1的多态性导致不同个体之间这种酯酶的水平和催化效率存在差异，这反过来表明不同个体可能更容易受到有机磷暴露的毒性影响。

Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of OP exposure.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

鉴定和使用：白芷素是从白芷（Angelica archangelica）果实中分离出的一种呋喃香豆素。它已被测试作为一种实验性药物。人体研究：白芷素在人类淋巴细胞中表现出光毒性和光致突变性。白芷素在体外的人类淋巴细胞中诱导结构染色体畸变和姐妹染色单体交换。动物研究：白芷素在小鼠中产生了抗惊厥效果。在大鼠中，用白芷素处理的大鼠肝脏没有观察到病变。白芷素在中国仓鼠V79细胞和小鼠C3H/1OT1/2细胞的乌本苷位点诱导突变。当在衣藻（Chlamydomonas reinhardii）中进行测试时，白芷素表现出光毒性和光致突变性。白芷素在Ames试验菌株（TA92、TA97、TA98、TA100）中表现出致突变性，但在TA94和TA102中未表现出。在TA98和TA100中的致突变性最高。微粒体活化不是致突变性的必要条件。当在体内和体外进行测试时，白芷素显示出抗炎和抗氧化活性。

IDENTIFICATION AND USE: Imperatorin is a furacoumarin isolated from fruits of Angelica archangelica. It has been tested as an experimental medication. HUMAN STUDIES: Imperatorin was phototoxic and the photomutagenic in human lymphocytes. Imperatorin induced structural chromosome aberrations and sister-chromatid exchanges in human lymphocytes in vitro. ANIMAL STUDIES: Imperatorin produced the anticonvulsant effect in mice. No lesions were observed in the livers of rats treated with imperatorin. Imperatorin induced mutations in Chinese hamster V79 cells and at the ouabain locus in mouse C3H/1OT1/2 cells. Imperatorin was phototoxic and photomutagenic when tested in Chlamydomonas reinhardii. Imperatorin was mutagenic in Ames tester strains (TA92, TA97, TA98, TA100), but not in TA94 and TA102. Mutagenicity was highest in TA98 and TA100. Microsomal activation was not required for mutagenicity. Imperatorin displayed anti-inflammatory and antioxidant activities when tested in vivo and in vitro.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

Imperatorin是一种胆碱酯酶或乙酰胆碱酯酶（AChE）抑制剂。胆碱酯酶抑制剂（或“抗胆碱酯酶”）抑制乙酰胆碱酯酶的作用。由于其基本功能，干扰乙酰胆碱酯酶作用的化学物质是强大的神经毒素，低剂量时会导致过度流涎和眼泪，随后是肌肉痉挛，最终导致死亡。神经气体和许多用于杀虫剂的物质已被证明通过结合乙酰胆碱酯酶活性位点的丝氨酸，完全抑制该酶。乙酰胆碱酯酶分解神经递质乙酰胆碱，该递质在神经和肌肉接头处释放，以使肌肉或器官放松。乙酰胆碱酯酶抑制的结果是乙酰胆碱积聚并继续发挥作用，以至于任何神经冲动不断传递，肌肉收缩不会停止。最常见的乙酰胆碱酯酶抑制剂之一是基于磷的化合物，它们被设计用来结合到酶的活性位点上。结构要求是一个磷原子带有两个亲脂性基团，一个离去基团（如卤素或硫氰酸盐）以及一个末端的氧。许多呋喃香豆素的作用机制基于它们与DNA和其他细胞成分如RNA、蛋白质以及膜中的几种蛋白质（如磷脂酶A2和C、钙依赖性和cAMP依赖性蛋白激酶和表皮生长因子）形成光加合物的能力。呋喃香豆素在DNA的碱基对之间插入，并在紫外线A照射后给出环加合物。（L579）。

Imperatorin is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen. The mechanism of action many furocoumarins is based on their ability to form photoadducts with DNA and other cellular components such as RNA, proteins, and several proteins found in the membrane such as phospholipases A2 and C, Ca-dependent and cAMPdependent protein-kinase and epidermal growth factor. Furocoumarins intercalate between base pairs of DNA and after ultraviolet-A irradiation, giving cycloadducts. (L579).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

未列入国际癌症研究机构(IARC)名录。IARC评估了其他呋喃香豆素类物质，将8-甲氧基补骨脂素归类为对人类致癌(第1组)，5-甲氧基补骨脂素归类为可能对人类致癌(第2A组)，以及其他某些呋喃香豆素类物质归类为对人类致癌性无法分类(第3组)。(L135)

Not listed by IARC. IARC has assessed other furocoumarins, classifying 8-methoxypsoralen as carcinogenic to humans (Group 1), 5-methoxypsoralen as possibly carcinogenic to humans (Group 2A), and certain other furocoumarins as not being classifiable as to their carcinogenicity to humans (Group 3). (L135)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

急性暴露于胆碱酯酶抑制剂可能会导致胆碱能危象，表现为严重的恶心/呕吐、流涎、出汗、心动过缓、低血压、晕厥和抽搐。肌肉无力可能会逐渐加重，如果呼吸肌肉受累，可能会导致死亡。在运动神经上乙酰胆碱的积累会导致神经肌肉接头处烟碱受体的过度刺激。当这种情况发生时，可能会出现肌肉无力、疲劳、肌肉痉挛、肌束颤动和麻痹等症状。当自主神经节上乙酰胆碱积累时，会导致交感系统中烟碱受体的过度刺激。与此相关的症状包括高血压和低血糖。由于乙酰胆碱的积累，在中枢神经系统中烟碱乙酰胆碱受体的过度刺激会导致焦虑、头痛、抽搐、共济失调、呼吸和循环抑制、震颤、全身无力，甚至可能陷入昏迷。当乙酰胆碱在毒蕈碱乙酰胆碱受体上过多时，表现出毒蕈碱过度刺激的症状，包括视觉障碍、胸部紧绷、由于支气管收缩引起的喘息、支气管分泌物增加、唾液分泌增加、流泪、出汗、蠕动和排尿。某些关于生育、生长和发育的生殖效应，特别是对男性和女性，已被特别与有机磷农药暴露联系起来。大多数关于生殖效应的研究都是在农村地区使用农药和杀虫剂的农民身上进行的。在女性中，月经周期紊乱、孕期延长、自然流产、死产以及后代的一些发育效应已被与有机磷农药暴露联系起来。产前暴露与胎儿生长和发育受损有关。神经毒性效应也与有机磷农药中毒有关，导致人类四种神经毒性效应：胆碱能综合征、中间综合征、有机磷诱导的迟发性多发性神经病（OPIDP）和慢性有机磷诱导的神经精神障碍（COPIND）。这些综合征是在急性 and 慢性暴露于有机磷农药后出现的。补骨脂素8-甲氧基补骨脂素对人体具有致癌性，5-甲氧基补骨脂素也可能如此（L135）。一些来自小鼠研究的证据表明，其他补骨脂素在与UVA辐射暴露结合时具有致癌性（A15105）。SKLM认为，食用含有典型量补骨脂素的食物，其浓度显著低于光毒性剂量范围，引起的皮肤癌额外风险是不显著的。然而，对于某些食物，尤其是芹菜和欧防风，由于储存、加工和生产条件的影响，可能会导致补骨脂素浓度显著增加，因此不能排除食用光毒性剂量的可能性（L2157）。补骨脂素光化学疗法已知会诱导多种副作用，包括红斑、水肿、色素沉着过度和皮肤过早老化。所有补骨脂素的光生物效应都源于它们的光化学反应。因为许多饮食或水溶性补骨脂素是细胞色素P450的强抑制剂，所以它们也会在与其他药物一起服用时引起不良反应。致癌效应的证据有限（L579）。

Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides. The furocoumarin 8-methoxypsoralen is carcinogenic to humans, and possibly 5-methoxypsoralen as well (L135). There is some evidence from mouse studies that other furocoumarins are carcinogenic when combined with exposure to UVA radiation (A15105). The SKLM regards the additional risk of skin cancer arising from the consumption of typical quantities of furocoumarin-containing foods, which remain significantly below the range of phototoxic doses, as insignificant. However, the consumption of phototoxic quantities cannot be ruled out for certain foods, particularly celery and parsnips, that may lead to significant increases in furocoumarin concentrations, depending on the storage, processing and production conditions. (L2157) Furocoumarin photochemotherapy is known to induce a number of side-effects including erythema, edema, hyperpigmentation, and premature aging of skin. All photobiological effects of furocoumarins result from their photochemical reactions. Because many dietary or water soluble furocoumarins are strong inhibitors of cytochrome P450s, they will also cause adverse drug reactions when taken with other drugs. Limited evidence of carcinogenic effect. (L579)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

低剂量暴露的症状包括过度流涎和眼泪。急性剂量症状包括严重恶心/呕吐、流涎、出汗、心动过缓、低血压、虚脱和抽搐。肌肉无力可能会逐渐加剧，如果呼吸肌肉受影响，可能会导致死亡。还可能出现高血压、低血糖、焦虑、头痛、震颤和共济失调。

Symptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result.

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

已经开发了一种用于血浆和组织中欧前胡素定量的快速敏感分析方法。通过气相色谱/质谱在选定离子监测模式下进行分析。获得的主要药代动力学参数为T(max) = 1.23 ± 0.26小时，C(max) = 0.95 ± 0.38微克/毫升，AUC = 3.42 ± 0.52小时微克/毫升和K(a) = 1.34 ± 0.18小时。实验结果表明，欧前胡素易于吸收，但其消除较慢，口服给药后3至12小时。欧前胡素在大鼠肝脏、肾脏、肺和心脏中的浓度高于其他器官。为了确定血清中的游离分数，使用截留分子量为10 kDa的超滤膜过滤样品，并使用液-液提取法提取。在大鼠血浆、自发性高血压大鼠血浆、人血浆和人血清白蛋白中的蛋白结合值分别为84 ± 3，69 ± 7，81 ± 7和75 ± 3%。

A rapid and sensitive assay for the quantification of imperatorin in plasma and tissues has been developed. An analysis was performed by gas chromatography/mass spectrometry in the selected ion-monitoring mode. The main pharmacokinetic parameters obtained were T(max) = 1.23 +/- 0.26 hr, C(max) = 0.95 +/- 0.38 ug/mL, AUC = 3.42 +/- 0.52 hr ug/mL and K(a) = 1.34 +/- 0.18 hr. The experimental results showed that imperatorin was easily absorbed, but its elimination was slow, from 3 to 12 hr after oral administration. The concentrations of imperatorin in rat liver, kidney, lung, and heart were higher than those in other organs. To determine the free fraction in serum, samples were filtered using ultrafiltration membranes with a molecular weight cut-off of 10 kDa, and extracted using liquid-liquid extraction. The protein binding values in rat plasma, spontaneous hypertensive rat plasma, human plasma and human serum albumin were 84 +/- 3, 69 +/- 7, 81 +/- 7 and 75 +/- 3%, respectively.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在本研究中，开发了一种简单灵敏的气相色谱-质谱方法，用于研究氧化欧前胡素在大鼠体内的生物利用度、蛋白结合以及代谢。结果显示，氧化欧前胡素在大鼠静脉注射和口服给药后的药代动力学呈现线性特征。氧化欧前胡素的绝对生物利用度分别计算为约3.85%、约33.51%和约34.76%，对应的给药剂量为6.25、12.5和25 mg/kg。氧化欧前胡素低生物利用度可能归因于吸收不良或广泛代谢。研究了氧化欧前胡素在大鼠肝微粒体体外形成的I相代谢物，并分离并鉴定出两种代谢物为花椒毒素和川楝素。口服给药氧化欧前胡素后，在大鼠血浆中检测到一种代谢物（川楝素），在大鼠尿液中检测到两种潜在代谢物（花椒毒素和川楝素）。然而，在大鼠粪便和胆汁中没有检测到潜在代谢物。结果表明，氧化欧前胡素的代谢物通过肾脏排出，川楝素与活性成分有关。去甲基化和氧化是主要的代谢途径。体外血浆蛋白结合实验表明，氧化欧前胡素在1.0和50.0 ug/mL的加标大鼠血浆浓度下的蛋白结合率分别为90.1%和92.6%，表明氧化欧前胡素在细胞内外空间的分布缓慢。

In this study, a simple and sensitive gas chromatography-mass spectrometry method was developed for the study of bioavailability and protein binding and the metabolism of imperatorin in rat. The results showed that the pharmacokinetics of imperatorin after intravenous and oral administration in rats exhibited linear characteristics. The absolute bioavailability of imperatorin was calculated as approximately 3.85, approximately 33.51 and approximately 34.76% for 6.25, 12.5 and 25 mg/kg, respectively. The low bioavailability of imperatorin may be attributed to the poor absorption or extensive metabolism. The phase I metabolites of imperatorin formed in vitro by rat liver microsomes were studied, and two metabolites were isolated and identified as xanthotoxol and heraclenin. Following oral administration of imperatorin, one metabolite (heraclenin) was detected in rat plasma, and two potential metabolites (xanthotoxol and heraclenin) were detected in rat urine. However, none of potential metabolites was detected in rat feces and bile. The results showed that the metabolites of imperatorin were excreted by kidney, and heraclenin was associated with an active component. Demethylation and oxygenization were the main metabolic pathways. In vitro plasma protein binding of imperatorin was 90.1 and 92.6% for the spiked rat plasma concentrations of 1.0 and 50.0 ug/mL, respectively, indicating that imperatorin showed slow distribution into the intra- and extracellular space.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 安全说明：
  S24/25
• WGK Germany：
  3
• 海关编码：
  29419090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  2-8°C

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product name : Imperatorin

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Section 2. HAZARDS IDENTIFICATION
Classification of the substance or mixture
Not a dangerous substance according to GHS.
This substance is not classified as dangerous according to Directive 67/548/EEC.
Label elements
The product does not need to be labelled in accordance with EC directives or respective national laws.
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Synonyms : 9-[(3-Methyl-2-buten-1-yl)oxy]-7h-furo[3,2-g][1]benzopyran-7-one
Ammidin
Marmelide
Marmelosin
NSC 402949
Formula : C16H14O4
Molecular Weight : 270,28 g/mol
CAS-No. EC-No. Index-No. Classification Concentration
9-(3-Methylbut-2-enyloxy)-7H-furo[3,2-g]chromen-7-one
482-44-0 207-581-1 - - -

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Section 4. FIRST AID MEASURES
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration.
In case of skin contact
Wash off with soap and plenty of water.
In case of eye contact
Flush eyes with water as a precaution.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water.

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Section 5. FIRE-FIGHTING MEASURES
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special protective equipment for fire-fighters
Wear self contained breathing apparatus for fire fighting if necessary.

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Section 6. ACCIDENTAL RELEASE MEASURES
Personal precautions
Avoid dust formation. Avoid breathing vapors, mist or gas.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
Sweep up and shovel. Keep in suitable, closed containers for disposal.

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Section 7. HANDLING AND STORAGE
Precautions for safe handling
Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire
protection.
Conditions for safe storage
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Recommended storage temperature: 2 - 8 °C

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Section 8. EXPOSURE CONTROLS/PERSONAL PROTECTION
Personal protective equipment
Respiratory protection
Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use
type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved
under appropriate government standards such as NIOSH (US) or CEN (EU).
Hand protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique (without
touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves
after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.
The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and the
standard EN 374 derived from it.
Eye protection
Use equipment for eye protection tested and approved under appropriate government standards such as
NIOSH (US) or EN 166(EU).
Skin and body protection
Choose body protection in relation to its type, to the concentration and amount of dangerous substances,
and to the specific work-place., The type of protective equipment must be selected according to the
concentration and amount of the dangerous substance at the specific workplace.
Hygiene measures
General industrial hygiene practice.

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Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Appearance
Form solid
Colour off-white, light brown
Safety data
pH no data available
Melting point 98 - 100 °C
Boiling point no data available
Flash point no data available
Ignition temperature no data available
Lower explosion limit no data available
Upper explosion limit no data available
Water solubility no data available
Partition coefficient: log Pow: 3,72
n-octanol/water

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Section 10. STABILITY AND REACTIVITY
Chemical stability
Stable under recommended storage conditions.
Conditions to avoid
no data available
Materials to avoid
Strong oxidizing agents
Hazardous decomposition products
Hazardous decomposition products formed under fire conditions. - Carbon oxides

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Section 11. TOXICOLOGICAL INFORMATION
Acute toxicity
no data available
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitization
no data available
Germ cell mutagenicity
no data available
Carcinogenicity
IARC: No component of this product present at levels greater than or equal to 0.1% is identified as
probable, possible or confirmed human carcinogen by IARC.
Reproductive toxicity
no data available
Specific target organ toxicity - single exposure
no data available
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Potential health effects
Inhalation May be harmful if inhaled. May cause respiratory tract irritation.
Ingestion May be harmful if swallowed.
Skin
May be harmful if absorbed through skin. May cause skin irritation.
Eyes May cause eye irritation.
Signs and Symptoms of Exposure
To the best of our knowledge, the chemical, physical, and toxicological properties have not been thoroughly
investigated.
Additional Information
RTECS: Not available

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Section 12. ECOLOGICAL INFORMATION
Toxicity
no data available
Persistence and degradability
no data available
Bioaccumulative potential
no data available
Mobility in soil
no data available
PBT and vPvB assessment
no data available
Other adverse effects
no data available

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Section 13. DISPOSAL CONSIDERATIONS
Product
Offer surplus and non-recyclable solutions to a licensed disposal company.
Contaminated packaging
Dispose of as unused product.

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Section 14. TRANSPORT INFORMATION
ADR/RID
Not dangerous goods
IMDG
Not dangerous goods
IATA
Not dangerous goods

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Section 15. REGULATORY INFORMATION
This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006.

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Section 16. OTHER INFORMATION
Further information
Copyright 2010 Co. License granted to make unlimited paper copies for internal use only.
The above information is believed to be correct but does not purport to be all inclusive and shall be used
only as a guide. The information in this document is based on the present state of our knowledge and is
applicable to the product with regard to appropriate safety precautions. It does not represent any guarantee
of the properties of the product. Co., shall not be held liable for any damage resulting from
handling or from contact with the above product. See reverse side of invoice or packing slip for additional
terms and conditions of sale.

制备方法与用途

简介

欧前胡素（imperatorin）和异欧前胡素（iso-imperatorin）属于6.7-呋喃香豆素类，广泛存在于多种植物中。它们具有抗菌、平喘及抗过敏等药理作用。

化学性质 来源

罗旦梅（Flacourtia jangomas, 属大风子科）的茎中可以提取欧前胡素。

用途

主要用于含量测定、鉴定和药理实验等。

应用 药理药效

• 抗菌：对多种细菌具有抑制作用。
• 平喘及抗过敏：能够缓解哮喘症状并对抗过敏反应。
• HIV研究：作为糠香豆素，广泛应用于HIV-1研究中。

生物活性 体内研究

• 抗焦虑和记忆改善：低剂量（10 mg/kg 和 20 mg/kg）的欧前胡素具有显著的抗焦虑效果，并能提高不同阶段的记忆与学习过程。
• 抗癫痫作用：30 和 40 mg/kg 的欧前胡素可增强卡马西平的抗癫痫效应，降低电击诱发惊厥的ED50值。
• 药效协同作用：高剂量（10 mg/kg）欧前胡素与卡马西平合用时，可以提高脑内卡马西平浓度。

体内作用机制

• 抑制谷氨酸转氨酶和乙酰胆碱酯酶活性。
• 改善顺扁桃碱（scopolamine, 1 mg/kg）引起的记忆障碍，并在重复给药下显著减轻这些影响。

化学特性

欧前胡素作为一种天然的呋喃香豆素，能够通过抑制细胞周期中G1期和cyclin D1表达来诱导人类急性髓性白血病细胞（HL-60）凋亡。此外，它还能有效监控HeLa 细胞中的转录水平抑制HIV-1复制，并具有潜在的治疗价值。

反应信息

• 作为反应物：
  描述：

  欧前胡素 在 溴 作用下， 以 溶剂黄146 为溶剂， 反应 5.0h， 以98%的产率得到5-bromo-8-hydroxypsoralen
  参考文献：
  名称：

  Kadry, H.; Osman, A. N.; Al-Azizi, M., Revue Roumaine de Chimie, 1992, vol. 37, # 8, p. 915 - 920

  摘要：

  DOI：
• 作为产物：
  描述：

  8-甲氧基补骨脂素 在 三溴化硼 、 sodium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 欧前胡素
  参考文献：
  名称：

  8-甲氧基补骨脂素的结构修饰物及其制备方 法与应用

  摘要：

  本发明公开了8‑甲氧基补骨脂素的结构修饰物及其制备方法与应用。本发明所提供的8‑甲氧基补骨脂素的结构修饰物为式1所示的化合物B20或式2所示的化合物A10。化合物B20在64μg/mL的浓度下对产肠毒素大肠杆菌的抑菌活性是8‑甲氧基补骨脂素的2.3倍；化合物A10在64μg/mL的浓度下对产肠毒素大肠杆菌的抑菌活性是8‑甲氧基补骨脂素的2.4倍。本发明的化合物B20和化合物A10可用于制备治疗和/或预防仔猪腹泻的药物。

  公开号：

  CN109503612B

文献信息

• CINAMIC COMPOUNDS AND DERIVATIVES THEREFROM FOR THE INHIBITION OF HISTONE DEACETYLASE
  申请人：Huang Chung-Yang

  公开号：US20100256401A1

  公开（公告）日：2010-10-07

  The invention relates to a compound represented by the following formula (I): and pharmaceutically acceptable salts, stereoisomers, enantiomers, prodrugs and solvates thereof. The compounds are useful as an agent for enhancing the neurite outgrowth and preventing or treating of diseases associated with HDAC in particular, tumor or cell proliferative diseases. In particular, the compounds of the invention can be used as an agent for anti-cancer, anti-diabetic, and anti-neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Spinocerebellar Ataxias (SCA), and human spinal muscular atrophy (SMA).

  该发明涉及以下式(I)所表示的化合物及其药学上可接受的盐、立体异构体、对映异构体、前药和溶剂合物。这些化合物可用作增强神经突起生长的药剂，并预防或治疗与HDAC特别相关的疾病，如肿瘤或细胞增殖性疾病。具体来说，该发明的化合物可用作抗癌、抗糖尿病和抗神经退行性疾病的药剂，如阿尔茨海默病、亨廷顿病、脊髓小脑共济失调（SCA）和人类脊髓肌肉萎缩症（SMA）的药剂。
• A simple one-step synthesis of phenyl ethers from phenyl acetates
  作者：Sunil K. Banerjee、Bishan D. Gupta、Kuber Singh

  DOI：10.1039/c39820000815

  日期：——

  Phenyl acetates when refluxed with alkyl halides in acetone solution in the presence of a crown ether and anhydrous potassium carbonate undergo alkylation yielding phenyl ethers.

  在冠醚和无水碳酸钾的存在下，乙酸苯酯与烷基卤在丙酮溶液中回流时，进行烷基化，生成苯基醚。
• [EN] MODULATORS OF THE P70S6 KINASE FOR USE IN THE TREATMENT OF BRAIN DISORDERS AND TRIPLE-NEGATIVE BREAST CANCER<br/>[FR] MODULATEURS DE LA P70S6 KINASE DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE TROUBLES CÉRÉBRAUX ET DU CANCER DU SEIN TRIPLE NÉGATIF
  申请人：SENTINEL ONCOLOGY LTD

  公开号：WO2016131776A1

  公开（公告）日：2016-08-25

  The invention provides compounds for use in the treatment of a disease or condition selected from brain disorders and triple-negative breast cancer, the compounds being of the formula (1) or a salt or tautomer thereof; wherein: X1 is N or N+(O'); X2 is N or CH; Q is selected from a C1-3 alkylene group, cyclopropane-1,1-diyl and cyclobutane- 1,1-diyl; R1 is selected from hydrogen and C1-4 alkyl;R2, R3 and R4 are the same or different and each is selected from hydrogen and fluorine; Ar1 is a benzene, thiophene, naphthyl or pyridine ring optionally substituted with 1, 2 or 3 substituents selected from fluorine; chlorine; bromine; CM hydrocarbyl; C1-4 hydrocarbyloxy; trifluoromethyl; difluoromethyl; cyano; trifluoromethoxy; difluoromethoxy; Ar2 is a monocyclic 5- or 6-membered heteroaryl ring containing 1, 2 or 3 heteroatom ring members selected from O, N and S and being optionally substituted with 1, 2 or 3 substituents selected from fluorine; C1-4 hydrocarbyl; amino; mono-C1-4 hydrocarbylamino and di-C1-4 hydrocarbylamino; and wherein, in each substituent consisting of or containing C1-4 hydrocarbyl, the C1-4 hydrocarbyl is selected from C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, cyclopropyl, cyclobutyl and cyclopropylmethyl.

  该发明提供了用于治疗脑部疾病和三阴性乳腺癌等疾病或症状的化合物，该化合物为以下公式（1）或其盐或互变异构体；其中：X1为N或N+(O')；X2为N或CH；Q从C1-3烷基、环丙烷-1,1-二基和环丁烷-1,1-二基中选择；R1从氢和C1-4烷基中选择；R2、R3和R4相同或不同，每个从氢和氟中选择；Ar1为苯、噻吩、萘或吡啶环，可选择地取代1、2或3个从氟、氯、溴、CM烃基、C1-4烃基氧、三氟甲基、二氟甲基、氰、三氟甲氧基、二氟甲氧基中选择的取代基；Ar2为含有1、2或3个来自O、N和S的杂原子环成员的单环5-或6-成员杂环环，可选择地取代1、2或3个从氟、C1-4烃基、氨基、单C1-4烃基氨基和双C1-4烃基氨基中选择的取代基；在每个由或含有C1-4烃基的取代基中，C1-4烃基从C1-4烷基、C2-4烯基、C2-4炔基、环丙基、环丁基和环丙基甲基中选择。
• NOVEL DERIVATIVES OF SINAPINIC ACID AND THE COSMETIC OR PHARMACEUTICAL USES THEREOF
  申请人：BASF Beauty Care Solutions France SAS

  公开号：US20150342847A1

  公开（公告）日：2015-12-03

  The present invention relates to a compound of general formula (I) below: in which: R 1 , R 2 and R 3 independently of one another represent a hydrogen atom; a C1-12 alkyl group; a C2-12 alkenyl group; a C2-12 alkynyl group; a C3-12 cycloalkyl group; a C1-12 acyl group; a sulfonyl group or a phosphonate group; represents a CH 2 —CH 2 group or a CH═CH group; n is an integer between 1 and 3; or a salt thereof. The invention further relates to a process for synthesizing this compound or salt, to a composition comprising it, to its cosmetic use, more particularly as a depigmenting agent and/or as a radical scavenger, to a cosmetic care process, and to its use as a drug, advantageously intended for preventing and/or treating pathological hyperpigmentation and/or inflammation.

  本发明涉及以下一般式（I）的化合物： 其中： R1、R2和R3分别独立地表示氢原子；C1-12烷基基团；C2-12烯基基团；C2-12炔基基团；C3-12环烷基基团；C1-12酰基团；磺酰基或膦酸酯基团；表示CH2— 基团或CH═CH基团；n是1到3之间的整数；或其盐。该发明还涉及合成该化合物或盐的过程，包括它的组合物，其化妆品用途，尤其作为脱色剂和/或自由基清除剂，化妆保养过程，以及其作为药物的用途，有利于预防和/或治疗病理性色素沉着和/或炎症。
• [EN] SUBSTITUTED QUINOXALINES AND BENZOTRIAZINE P70S6 KINASE INHIBITORS<br/>[FR] INHIBITEURS DE TYPE QUINOXALINES ET BENZOTRIAZINE SUBSTITUÉES DE LA P70S6 KINASE
  申请人：SENTINEL ONCOLOGY LTD

  公开号：WO2016170163A1

  公开（公告）日：2016-10-27

  The invention provides compounds that inhibit or modulate the activity of p70S6 kinase, the compounds being of the formula (0), or a salt, tautomer or N-oxide thereof; wherein: X1 is N or N+(0-); X2 is N or CH; Q1 is an optionally substituted C1-8 alkylene; Q2 is a bond or an optionally substituted C1-8 alkylene group; R1 is selected from hydrogen and a group Cy1; Cy1 is an optionally substituted 4 to 7 membered monocyclic non-aromatic carbocyclic or heterocyclic group containing 0, 1 or 2 heteroatom ring members selected from O and S and oxidised forms of S; R2, R3 and R4 are the same or different and each is selected from hydrogen, fluorine, chlorine, C1-2 alkyl and C1-2 alkoxy, wherein each C1-2 alkyl and C1-2 alkoxy is optionally substituted with two or more fluorine atoms; Ar1 is an optionally substituted monocyclic 5 or 6-membered aryl or heteroaryl ring containing 0, 1 or 2 heteroatom ring members selected from O, N and S, or a naphthyl ring Ar2 is an optionally substituted bicyclic 8 to 1 1 -membered heteroaryl group containing 1, 2, 3 or 4 heteroatom ring members selected from O, N and S. The compounds are useful in medicine, for example in the treatment of a disease or condition selected from cancers (e.g. triple negative breast cancer, brain tumours and brain metastases arising from non-brain cancers), neurodevelopmental diseases (e.g. Fragile X syndrome) and neurodegenerative diseases.

  该发明提供了抑制或调节p70S6激酶活性的化合物，该化合物的结构如下式（0），或其盐、互变异构体或N-氧化物；其中：X1为N或N+(0-)；X2为N或CH；Q1为可选择取代的C1-8烷基；Q2为键或可选择取代的C1-8烷基基团；R1选自氢和Cy1基团；Cy1为可选择取代的含有0、1或2个来自O和S的杂原子环成员的4到7成员单环非芳香碳环或杂环基团及S的氧化形式；R2、R3和R4相同或不同，每个选自氢、氟、氯、C1-2烷基和C1-2烷氧基，其中每个C1-2烷基和C1-2烷氧基可选择地取代为两个或更多氟原子；Ar1为可选择取代的含有0、1或2个来自O、N和S的杂原子环成员的单环5或6成员芳基或杂芳基环，或一个萘环；Ar2为可选择取代的含有1、2、3或4个来自O、N和S的杂原子环成员的双环8到11成员杂芳基基团。这些化合物在医学上有用，例如在治疗癌症（如三阴性乳腺癌、脑肿瘤和来自非脑部癌症的脑转移瘤）、神经发育疾病（如脆性X综合征）和神经退行性疾病等疾病或病况的治疗中。

表征谱图