N-花生四烯酰对氨基苯酚 | 183718-77-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-花生四烯酰对氨基苯酚
• 中文别名: 对花生四烯酰氨基酚；N-(4-羟基苯)花生四烯酸酰胺；N-(4-羟基苯基)花生四烯酰胺
• 英文名称: AM 404
• 英文别名: N-arachidonoylphenolamine；N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide；N-(4-hydroxyphenyl)-arachidonoylamide；(5Z,8Z,11Z,14Z)-N-(4-hydroxyphenyl)icosa-5,8,11,14-tetraen amide；N-(4-hydroxyphenyl)-arachidonylamide；N-arachidonoyl aminophenol；(5Z,8Z,11Z,14Z)-N-(4-hydroxyphenyl)icosa-5,8,11,14-tetraenamide
• CAS: 183718-77-6
• 化学式: C₂₆H₃₇NO₂
• 分子量: 395.585
• InChiKey: IJBZOOZRAXHERC-DOFZRALJSA-N

物化性质

• 沸点：
  579.4±50.0 °C(Predicted)
• 密度：
  1.007±0.06 g/cm3(Predicted)
• 闪点：
  14 °C
• 溶解度：
  乙醇：24 mg/mL光敏溶液。

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  29
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 危险品标志：
  F
• 危险类别码：
  R36/37/38
• 危险品运输编号：
  UN 1170 3/PG 2
• WGK Germany：
  1
• 安全说明：
  S7
• 储存条件：
  -20°C，密闭保存，并保持干燥。

SDS

---

SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : N-(4-Hydroxyphenyl)-arachidonylamide
REACH No. : A registration number is not available for this substance as the substance
or its uses are exempted from registration, the annual tonnage does not
require a registration or the registration is envisaged for a later
registration deadline.
CAS-No. : 183718-77-6
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

---

SECTION 2: Hazards identification
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008
Flammable liquids (Category 2), H225
For the full text of the H-Statements mentioned in this Section, see Section 16.
Classification according to EU Directives 67/548/EEC or 1999/45/EC
F Highly flammable R11
For the full text of the R-phrases mentioned in this Section, see Section 16.
Label elements
Labelling according Regulation (EC) No 1272/2008
Pictogram
Signal word Danger
Hazard statement(s)
H225 Highly flammable liquid and vapour.
Precautionary statement(s)
P210 Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
Supplemental Hazard none
Statements
According to European Directive 67/548/EEC as amended.
Hazard symbol(s) F Highly flammable
R-phrase(s)
R11 Highly flammable.
S-phrase(s)
S16 Keep away from sources of ignition - No smoking.
Caution - this mixture contains a substance not yet fully tested.
Other hazards - none

---

SECTION 3: Composition/information on ingredients
Mixtures
Synonyms : AM404
Formula : C26H37NO2 C26H37NO2
Molecular Weight : 395,58 g/mol
No components need to be disclosed according to the applicable regulations.
For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16

---

SECTION 4: First aid measures
Description of first aid measures
General advice
Consult a physician. Show this safety data sheet to the doctor in attendance.
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
In case of skin contact
Wash off with soap and plenty of water. Consult a physician.
In case of eye contact
Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.
If swallowed
Do NOT induce vomiting. Never give anything by mouth to an unconscious person. Rinse mouth with
water. Consult a physician.
Most important symptoms and effects, both acute and delayed
The most important known symptoms and effects are described in the labelling (see section 2.2) and/or in
section 11
Indication of any immediate medical attention and special treatment needed
no data available

---

SECTION 5: Firefighting measures
Extinguishing media
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, nitrogen oxides (NOx)
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
Use water spray to cool unopened containers.

---

SECTION 6: Accidental release measures
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid breathing vapors, mist or gas. Ensure adequate ventilation.
Remove all sources of ignition. Evacuate personnel to safe areas. Beware of vapours accumulating to
form explosive concentrations. Vapours can accumulate in low areas.
For personal protection see section 8.
Environmental precautions
Prevent further leakage or spillage if safe to do so. Do not let product enter drains.
Methods and materials for containment and cleaning up
Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and
place in container for disposal according to local regulations (see section 13).
Reference to other sections
For disposal see section 13.

---

SECTION 7: Handling and storage
Precautions for safe handling
Avoid contact with skin and eyes. Avoid inhalation of vapour or mist.
Keep away from sources of ignition - No smoking.Take measures to prevent the build up of electrostatic
charge.
For precautions see section 2.2.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place. Containers which are
opened must be carefully resealed and kept upright to prevent leakage.
Recommended storage temperature: -20 °C
Specific end use(s)
A part from the uses mentioned in section 1.2 no other specific uses are stipulated

---

SECTION 8: Exposure controls/personal protection
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and
at the end of workday.
Personal protective equipment
Eye/face protection
Face shield and safety glasses Use equipment for eye protection tested and approved under
appropriate government standards such as NIOSH (US) or EN 166(EU).
Skin 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.
Body Protection
Impervious clothing., Flame retardant antistatic protective clothing, The type of protective
equipment must be selected according to the concentration and amount of the dangerous
substance at the specific workplace.
Respiratory protection
Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator
with multi-purpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup
to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air
respirator. Use respirators and components tested and approved under appropriate government
standards such as NIOSH (US) or CEN (EU).
Control of environmental exposure
Prevent further leakage or spillage if safe to do so. Do not let product enter drains.

---

SECTION 9: Physical and chemical properties
Information on basic physical and chemical properties
a) Appearance Form: liquid
b) Odour no data available
c) Odour Threshold no data available
d) pH no data available
e) Melting point/freezing no data available
point
f) Initial boiling point and no data available
boiling range
g) Flash point 14 °C - closed cup
h) Evaporation rate no data available
i) Flammability (solid, gas) no data available
j) Upper/lower no data available
flammability or
explosive limits
k) Vapour pressure no data available
l) Vapour density no data available
m) Relative density no data available
n) Water solubility no data available
o) Partition coefficient: n- no data available
octanol/water
p) Auto-ignition no data available
temperature
q) Decomposition no data available
temperature
r) Viscosity no data available
s) Explosive properties no data available
t) Oxidizing properties no data available
Other safety information
no data available

---

SECTION 10: Stability and reactivity
Reactivity
no data available
Chemical stability
Stable under recommended storage conditions.
Possibility of hazardous reactions
no data available
Conditions to avoid
Heat, flames and sparks. Extremes of temperature and direct sunlight.
Incompatible materials
Oxidizing agents, Alkali metals, Ammonia, Peroxides
Hazardous decomposition products
Other decomposition products - no data available
In the event of fire: see section 5

---

SECTION 11: Toxicological information
Information on toxicological effects
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
Additional Information
RTECS: Not available
Central nervous system depression, narcosis, Nausea, Dizziness, Damage to the heart., To the best of our
knowledge, the chemical, physical, and toxicological properties have not been thoroughly investigated.
Heart - Irregularities - Based on Human Evidence

---

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
Results of PBT and vPvB assessment
PBT/vPvB assessment not available as chemical safety assessment not required/not conducted
Other adverse effects
no data available

---

SECTION 13: Disposal considerations
Waste treatment methods
Product
Burn in a chemical incinerator equipped with an afterburner and scrubber but exert extra care in igniting
as this material is highly flammable. Offer surplus and non-recyclable solutions to a licensed disposal
company.
Contaminated packaging
Dispose of as unused product.

---

SECTION 14: Transport information
UN number
ADR/RID: 1170 IMDG: 1170 IATA: 1170
UN proper shipping name
ADR/RID: ETHANOL
IMDG: ETHANOL
IATA: Ethanol
Transport hazard class(es)
ADR/RID: 3 IMDG: 3 IATA: 3
Packaging group
ADR/RID: II IMDG: II IATA: II
Environmental hazards
ADR/RID: no IMDG Marine Pollutant: no IATA: no
Special precautions for user
no data available

---

---

SECTION 15 - REGULATORY INFORMATION
N/A

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

AM404是一种内源性大麻素再摄取抑制剂，在低微摩尔范围内能够阻断阿难酰胺的IC50值运输。该化合物能松弛用苯肾上腺素收缩的大鼠离体肝动脉，其pEC50值为7.4（对应于0.04µM的EC50），具有神经保护作用。

反应信息

• 作为产物：
  描述：

  花生四烯酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 1.25h， 生成 N-花生四烯酰对氨基苯酚
  参考文献：
  名称：

  内源性大麻素配体花生四烯基乙醇酰胺的头基类似物。

  摘要：

  合成了内源性大麻素的几种类似物花生四烯基乙醇酰胺（anandamide），以研究乙醇酰胺首基的结构要求。通过标准的受体结合测定法，使用tri化的CP-55,940作为放射性配体，评估了类似物的CB1受体亲和力，并与Kan为78 nM的anandamide进行了比较。用硫原子取代酰胺羰基氧对CB1亲和力有不利影响。anandamide和（R）-methanandamide的硫代类似物对CB1的亲和力很弱。还显示了酰胺氮的次要性质对于亲和力很重要，表明酰胺NH与受体之间可能存在氢键相互作用。在头部基团中引入酚部分会导致受体亲和力的损失，除非在the基氮和酚之间引入亚甲基间隔基。还使用小鼠脾制剂测试了一组类似物对CB2受体的亲和力，发现它们对CB2位点的亲和力低。值得注意的是，anandamide和（R）-methanandamide对CB1受体表现出很高的选择性。总体而言，此处提供的数据表明，

  DOI：

  10.1021/jm960152y

文献信息

• New Analgesics Synthetically Derived from the Paracetamol Metabolite <i>N</i>-(4-Hydroxyphenyl)-(5<i>Z</i>,8<i>Z</i>,11<i>Z</i>,14<i>Z</i>)-icosatetra-5,8,11,14-enamide
  作者：Christian Sinning、Bernhard Watzer、Ovidiu Coste、Rolf M. Nüsing、Ingo Ott、Alessia Ligresti、Vincenzo Di Marzo、Peter Imming

  DOI：10.1021/jm800807k

  日期：2008.12.25

  N-(4-hydroxyphenyl)-(5Z,8Z,11Z,14Z)-icosatetra-5,8,11,14-enamide (AM404) is a metabolite of the well-known analgesic paracetamol. AM404 inhibits endocannabinoid cellular uptake, binds weakly to CB1 and CB2 cannabinoid receptors, and is formed by fatty acid amide hydrolase (FAAH) in vivo. We prepared three derivatives of this new (endo)cannabinoid using bioisosteric replacement (1), homology (2), and derivatization (3)

  N-（4-羟基苯基）-（5Z，8Z，11Z，14Z）-二十碳五，8,11,14-酰胺（AM404）是众所周知的止痛药扑热息痛的代谢产物。AM404抑制内源性大麻素的细胞摄取，与CB1和CB2大麻素受体弱结合，并由体内的脂肪酸酰胺水解酶（FAAH）形成。我们使用AM404中4-氨基苯酚部分的生物立体置换（1），同源性（2）和衍生化（3），制备了这种新的（内切）大麻素的三种衍生物，并针对CB1，CB2和FAAH进行了测试。我们发现对两种大麻素受体的亲和力等于或大于AM404。从C20到C2的酰基链缩短导致了三个新的扑热息痛类似物：N-（1H-吲唑-5-基）乙酰胺（5），N-（4-羟基苄基）乙酰胺（6）和N-（4-羟基-3-甲氧基苯基）乙酰胺（7）。同样，分别针对CB1，CB2、5、6和7进行了测试，和FAAH，没有明显的活动。但是，在全血测定中，5和7表现得像环氧合酶抑制剂。最后，在小鼠福尔马林测试中，5（50
• Synthesis of Acetaminophen Analogues Containing α-Amino Acids and Fatty Acids for Inhibiting Hepatotoxicity
  作者：Seunghee Jung、Yuya Kawashima、Takuya Noguchi、Nobuyuki Imai

  DOI：10.1055/s-0037-1611893

  日期：2019.10

  reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI). We have obtained acetaminophen analogues in 57–99% yields by using aniline derivatives with protected α-amino acids and fatty acids via the corresponding mixed carbonic carboxylic anhydrides in aqueous MeCN. We have also succeeded in synthesizing AM404 analogues in 76–97% yields, which are expected to be promising candidates for reducing hepatotoxicity

  献给EJ科里教授在他的90之际个生日。 抽象的 对乙酰氨基酚是一种流行的解热镇痛药，与非甾体类抗炎药（NSAIDs）相比，抗炎作用弱，副作用发生率低。然而，对乙酰氨基酚由于反应性代谢产物N-乙酰基-对苯醌亚胺（NAPQI）而引起肝毒性。通过在水性MeCN中通过相应的混合碳羧酸酐使用受保护的α-氨基酸和脂肪酸的苯胺衍生物，我们以57-99％的产率获得了对乙酰氨基酚类似物。我们还成功地以76–97％的产率合成了AM404类似物，有望降低肝毒性。 对乙酰氨基酚是一种流行的解热镇痛药，与非甾体类抗炎药（NSAIDs）相比，抗炎作用弱，副作用发生率低。然而，对乙酰氨基酚由于反应性代谢产物N-乙酰基-对苯醌亚胺（NAPQI）而引起肝毒性。通过在水性MeCN中通过相应的混合碳羧酸酐使用受保护的α-氨基酸和脂肪酸的苯胺衍生物，我们以57-99％的产率获得了对乙酰氨基酚类似物。我们还成功地以76–97％的产
• Dual modulation of endocannabinoid transport and fatty-acid amide hydrolase for treatment of excitotoxicity
  申请人：Bahr Ben A.

  公开号：US20100234379A1

  公开（公告）日：2010-09-16

  The endocannabinoid transporter and FAAH are sites of modulation that allow pharmacological enhancement of protective endocannabinergic signals. Selective inhibitors of the transporter and inhibitors of FAAH caused additive augmentation of endogenous signaling events mediated by the cannabinoid CB1 receptor. Disruption of such signals has been shown to prevent neuronal maintenance processes and increase vulnerability to brain damage. Here, blocking endocannabinoid inactivation enhanced cannabinergic activity and ameliorated cellular disturbances associated with excitotoxicity. Modulating the endocannabinoid system in this way also prevented excitotoxic behavioral abnormalities including memory impairment. Collectively, these results indicate that increasing endocannabinoid responses by inhibiting the endocannabinoid transported and/or the inhibiting FAAH leads to molecular, cellular, and functional protection against excitotoxic insults like stroke and traumatic brain injury.

  内源大麻素转运体和FAAH是调节的位点，允许药物增强保护性内源大麻素信号。选择性转运体抑制剂和FAAH抑制剂导致通过大麻素CB1受体介导的内源信号事件的加成增强。破坏这种信号已被证明可以防止神经维持过程并增加对脑损伤的脆弱性。在这里，阻断内源大麻素失活增强了大麻活性，并改善了与兴奋毒性相关的细胞紊乱。以这种方式调节内源大麻素系统还可以预防兴奋毒性行为异常，包括记忆障碍。总的来说，这些结果表明，通过抑制内源大麻素转运体和/或抑制FAAH来增加内源大麻素反应，可以在分子、细胞和功能上保护免受像中风和创伤性脑损伤等兴奋毒性侵害。
• A Convenient Protocol for the Synthesis of Fatty Acid Amides
  作者：Jens Nolsøe、Silje Johansson、Tonje Johannessen、Christiane Ellefsen、Mali Ristun、Simen Antonsen、Trond Hansen、Yngve Stenstrøm

  DOI：10.1055/s-0037-1611939

  日期：2019.1

  Several classes of biologically occurring fatty acid amides have been reported from mammalian and plant sources. Many amides conjugated with fatty acids of mammalian origin exhibit specific activation of individual receptors. Their potential as pharmacological tools or as lead compounds towards the development of novel therapeutics is of great interest. Hence, access to such amides by a practical,

  已经从哺乳动物和植物来源报道了几类生物存在的脂肪酸酰胺。许多与哺乳动物来源的脂肪酸结合的酰胺表现出对个体受体的特异性激活。它们作为药理学工具或作为开发新疗法的先导化合物的潜力引起了人们极大的兴趣。因此，需要在不影响敏感功能的几何形状或位置的情况下，通过实用、高产和可扩展的协议来获取此类酰胺。满足所有这些要求的方案包括用羰基二咪唑 (CDI) 活化相应的酸，然后与所需的胺或其盐酸盐反应。已经以通常高产率制备了五十多种化合物。
• Inhibitor of endocannabinoid cellular reuptake
  申请人：University of Bern

  公开号：US10414721B1

  公开（公告）日：2019-09-17

  Provided is a highly potent and selective endocannabioid cellular reuptake inhibitor represented by formula (I): or a pharmaceutically acceptable solvate or co-crystal thereof as well as to a formulation comprising this inhibitor, and to methods of treatment in which this inhibitor is used.

  提供了一种高效且选择性的内源大麻素细胞摄取抑制剂，其化学式表示为（I）：或其药学上可接受的溶剂或共晶体，以及包含该抑制剂的配方，以及使用该抑制剂的治疗方法。