阿西美辛 | 53164-05-9

• 物质功能分类: 原料药 - 解热镇痛药 - 非甾抗炎药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 阿西美辛
• 中文别名: 1-(4-氯苯甲酰基)-5-甲氧基-2-甲基吲哚-3-乙酸羧甲基酯；1-(4-氯苯甲酰基)-5-甲氧基-2-甲基-1H-吲哚-3-乙酸羧甲酯；[1-(4-氯苯甲酰基)-5-甲氧基-2-甲基吲哚-3-基]乙酰氧基乙酸；[1-(对氯苯甲酰基)-5-甲；炎痛美新；1-(对氯苯甲酰基)-5-甲氧基-2-甲基吲哚-3-乙酸羧甲酯；1-(4-氯苯甲酰基)-5-甲氧基-2-甲基-1H-吲哚-3-乙酸羧甲基酯
• 英文名称: acemetacin
• 英文别名: 2-(2-(1-((4-Chlorophenyl)carbonyl)-5-methoxy-2-methylindol-3-yl)acetyloxy)acetic Acid；2-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetoxy)acetic acid；2-[2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetyl]oxyacetic acid；{[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetoxy}acetic acid；acemethacine
• CAS: 53164-05-9
• 化学式: C₂₁H₁₈ClNO₆
• mdl: MFCD00151473
• 分子量: 415.83
• InChiKey: FSQKKOOTNAMONP-UHFFFAOYSA-N

物化性质

• 熔点：
  151.5°C
• 沸点：
  565.5±50.0 °C(Predicted)
• 密度：
  1.2387 (rough estimate)
• 溶解度：
  几乎不溶于水，溶于丙酮，微溶于无水乙醇。
• 碰撞截面：
  191 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  94.8
• 氢给体数：
  1
• 氢受体数：
  6

ADMET

代谢

Acemetacin是一种高度代谢的药物，通过酯水解断裂形成其主要和活性代谢物吲哚美辛。它还产生了其他非活性代谢物，这些代谢物是通过O-脱甲基化、N-脱酰基化反应生成的，其中一部分还会与葡萄糖醛酸结合转化。

Acemetacin is highly metabolized and degraded by esterolytic cleavage to form its major and active metabolite indometacin. It presents other inactive metabolites made by reaction of O-demethylation, N-desacylation and part of them are also transformed by conjugation with glucuronic acid.

来源:DrugBank

毒理性

• 蛋白质结合

Acemetacin与血浆蛋白高度结合，结合率超过90%。

Acemetacin is found highly bound to plasma proteins, reaching a percentage higher than 90% of the administered dose.

来源:DrugBank

吸收、分配和排泄

• 吸收

在连续8天每天两次口服阿塞美辛后，老年组的Cmax达到276.8 ng/ml，而年轻组为187 ng/ml，存在年龄依赖性。同时，Tmax为2.5小时，AUC的范围在483-712 ng·h/ml之间。阿塞美辛在重复剂量后的生物利用度大约为血浆中的66%，尿液中的64%。

After 8 days of oral administration twice daily of acemetacin there was an age-dependant Cmax of 276.8 ng/ml in elderly compared to 187 ng/ml for younger individuals. There was also a Tmax of 2.5 h and AUC in a range of 483-712 ng h/ml. The bioavailability of acemetacin after repeated doses is aproximately 66% in plasma and 64% in urine.

来源:DrugBank

吸收、分配和排泄

• 消除途径

阿西美辛的消除分为肾消除，占总给药剂量的40%，剩余的60%通过粪便排出。

The elimination of acemetacin is divided in renal elimination that covers 40% of the complete administered dose and the restant 60% is excreted in feces.

来源:DrugBank

吸收、分配和排泄

• 分布容积

阿西美辛的表观分布容积在0.5-0.7升/公斤的范围内。

The apparent volume of distribution of acemetacin is in a range of 0.5-0.7 L/kg.

来源:DrugBank

吸收、分配和排泄

• 清除

静脉给药时，阿西美辛在健康受试者体内的清除率为4.59毫升/分钟/千克。

Intravenous administration of acemetacin in healthy subjects reported a clearance rate of 4.59 ml min/kg.

来源:DrugBank

安全信息

• 危险等级：
  6.1(a)
• 危险品标志：
  T+
• 安全说明：
  S22,S25,S36/37/39,S45
• 危险类别码：
  R26/27/28
• WGK Germany：
  3
• 海关编码：
  2942000000
• 危险品运输编号：
  UN 2811
• 包装等级：
  II
• 危险类别：
  6.1(a)
• 危险性防范说明：
  P260,P264,P280,P284,P301+P310,P302+P350
• 危险性描述：
  H300,H310,H330
• 储存条件：
  -20°C 冰箱

SDS

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SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : Acemetacin
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. : 53164-05-9
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
Acute toxicity, Inhalation (Category 1), H330
Acute toxicity, Dermal (Category 2), H310
Acute toxicity, Oral (Category 2), H300
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
T+ Very toxic R26/27/28
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)
H300 Fatal if swallowed.
H310 Fatal in contact with skin.
H330 Fatal if inhaled.
Precautionary statement(s)
P260 Do not breathe dust/ fume/ gas/ mist/ vapours/ spray.
P264 Wash hands thoroughly after handling.
P280 Wear protective gloves/ protective clothing.
P284 Wear respiratory protection.
P302 + P350 IF ON SKIN: Gently wash with plenty of soap and water.
P310 Immediately call a POISON CENTER or doctor/ physician.
Supplemental Hazard none
Statements
Other hazards - none

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SECTION 3: Composition/information on ingredients
Substances
Chemical characterization : Natural product
Synonyms : 1-(p-Chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid
carboxymethyl ester
Formula : C21H18ClNO6
Molecular Weight : 415,82 g/mol
CAS-No. : 53164-05-9
EC-No. : 258-403-4
Hazardous ingredients according to Regulation (EC) No 1272/2008
Component Classification Concentration
Acemetacin
CAS-No. 53164-05-9 Acute Tox. 1; Acute Tox. 2; <= 100 %
EC-No. 258-403-4 H300, H310, H330
Hazardous ingredients according to Directive 1999/45/EC
Component Classification Concentration
Acemetacin
CAS-No. 53164-05-9 T+, R26/27/28 <= 100 %
EC-No. 258-403-4
For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16

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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. Take victim immediately to hospital. Consult a physician.
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. 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

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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), Hydrogen chloride gas
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

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SECTION 6: Accidental release measures
Personal precautions, protective equipment and emergency procedures
Wear respiratory protection. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure
adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.
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
Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed
containers for disposal.
Reference to other sections
For disposal see section 13.

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SECTION 7: Handling and storage
Precautions for safe handling
Avoid contact with skin and eyes. Avoid formation of dust and aerosols.
Provide appropriate exhaust ventilation at places where dust is formed.Normal measures for preventive fire
protection.
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.
Specific end use(s)
Apart from the uses mentioned in section 1.2 no other specific uses are stipulated

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SECTION 8: Exposure controls/personal protection
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling
the product.
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.
Full contact
Material: Nitrile rubber
Minimum layer thickness: 0,11 mm
Break through time: 480 min
Material tested:Dermatril® (KCL 740 / Z677272, Size M)
Splash contact
Material: Nitrile rubber
Minimum layer thickness: 0,11 mm
Break through time: 480 min
Material tested:Dermatril® (KCL 740 / Z677272, Size M)
data source: KCL GmbH, D-36124 Eichenzell, phone [phone], test method: EN374
If used in solution, or mixed with other substances, and under conditions which differ from EN 374,
contact the supplier of the CE approved gloves. This recommendation is advisory only and must
be evaluated by an industrial hygienist and safety officer familiar with the specific situation of
anticipated use by our customers. It should not be construed as offering an approval for any
specific use scenario.
Body Protection
Complete suit protecting against chemicals, 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 particle
respirator type N100 (US) or type P3 (EN 143) 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.

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SECTION 9: Physical and chemical properties
Information on basic physical and chemical properties
a) Appearance Form: solid
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 no data available
h) Evapouration 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

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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
no data available
Incompatible materials
no data available
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
LD50 Oral - rat - 24,2 mg/kg
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitisation
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: NL3521400
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.

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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
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
Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed
professional waste disposal service to dispose of this material. Dissolve or mix the material with a
combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.
Contaminated packaging
Dispose of as unused product.

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SECTION 14: Transport information
UN number
ADR/RID: 2811 IMDG: 2811 IATA: 2811
UN proper shipping name
ADR/RID: TOXIC SOLID, ORGANIC, N.O.S. (Acemetacin)
IMDG: TOXIC SOLID, ORGANIC, N.O.S. (Acemetacin)
IATA: Toxic solid, organic, n.o.s. (Acemetacin)
Transport hazard class(es)
ADR/RID: 6.1 IMDG: 6.1 IATA: 6.1
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

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SECTION 15: Regulatory information
This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006.
Safety, health and environmental regulations/legislation specific for the substance or mixture
no data available
Chemical Safety Assessment
For this product a chemical safety assessment was not carried out

---

SECTION 16: Other information
Full text of H-Statements referred to under sections 2 and 3.
Acute Tox. Acute toxicity
H300 Fatal if swallowed.
H310 Fatal in contact with skin.
H330 Fatal if inhaled.
Full text of R-phrases referred to under sections 2 and 3
T+ Very toxic
R26/27/28 Very toxic by inhalation, in contact with skin and if swallowed.
Further information
Copyright 2014 Co. LLC. 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. Corporation and its Affiliates shall not be held
liable for any damage resulting from handling or from contact with the above product. See
and/or the reverse side of invoice or packing slip for additional terms and conditions of sale.

制备方法与用途

根据您提供的信息，阿西美辛的制备涉及多个合成步骤。以下是对这些步骤的简要概述：

1. 起始原料：

   • 对甲氧基苯肼
   • (3-乙酰基丙酰氧基)乙酸苄酯

2. 方法一（主要路线）：

   1. 将对甲氧基苯肼与(3-乙酰基丙酰氧基)乙酸苄酯反应生成化合物II。
   2. 化合物II与对氯苯甲酰氯在乙酸中进行环化反应，生成化合物III。
   3. 化合物III还原为阿西美辛。

3. 方法二：

   1. 对甲氧基苯肼直接与(3-乙酰基丙酰氧基)乙酸苄酯在乙酸中进行环化反应，制备得到化合物I。
   2. 化合物I还原为阿西美辛。

4. 方法三：

   1. 对甲氧基苯肼和(3-乙酰基丙酰氧基)乙酸苄酯先环合成化合物IV。
   2. 将化合物IV与对氯苯甲酰氯进行反应生成化合物I。
   3. 化合物I还原为阿西美辛。

5. 方法四：

   1. 同样地，对甲氧基苯肼和(3-乙酰基丙酰氧基)乙酸苄酯先环合成化合物IV。
   2. 将化合物IV与对氯苯甲酰氯进行反应生成化合物I。
   3. 化合物I还原为阿西美辛。

注意事项：

1. 阿西美辛属于剧毒物品，处理时需严格遵守安全操作规程，并在通风良好的环境下进行。
2. 合成过程中会产生有毒气体（如氮氧化物、氯化物烟雾），需要采取适当的通风和防护措施。
3. 库房应保持低温干燥条件以防止副反应发生。

这些合成路线中，主要的化学反应包括酰基化、环合、还原等步骤。具体实验操作时，请参考相关文献并确保所有安全措施到位。

反应信息

• 作为反应物：
  描述：

  阿西美辛 在 sodium hydroxide 、 盐酸羟胺 、 盐酸 、 三氯化铁 作用下， 生成 4-氯-N-羟基苯甲酰胺
  参考文献：
  名称：

  Zinner; Gruenefeld, Johann; Gevensleben, Pharmazie, 2003, vol. 58, # 6, p. 431 - 432

  摘要：

  DOI：
• 作为产物：
  描述：

  吲哚美辛 在 palladium on activated charcoal 氢气 、 potassium carbonate 作用下， 以 乙酸乙酯 为溶剂， 反应 4.75h， 生成 阿西美辛
  参考文献：
  名称：

  Boltze; Brendler; Jacobi, Arzneimittel-Forschung/Drug Research, 1980, vol. 30, # 8 A, p. 1314 - 1325

  摘要：

  DOI：

文献信息

• Eflornithine Prodrugs, Conjugates and Salts, and Methods of Use Thereof
  申请人：Xu Feng

  公开号：US20100120727A1

  公开（公告）日：2010-05-13

  In one aspect, the present invention provides a composition of a covalent conjugate of an eflornithine analog with an anti-inflammatory drug. In another aspect, the present invention provides a composition of an eflornithine prodrug. In another aspect, the present invention provides a composition of an eflornithine or its derivatives aspirin salt. In another aspect, the present invention provides methods for treating or preventing cancer using the conjugates or salts of eflornithine analogs or eflornithine prodrugs.

  在一个方面，本发明提供了一种氟硝西汀类似物与抗炎药物的共价结合物的组合物。在另一个方面，本发明提供了一种氟硝西汀前药的组合物。在另一个方面，本发明提供了一种氟硝西汀或其衍生物水杨酸盐的组合物。在另一个方面，本发明提供了使用氟硝西汀类似物或氟硝西汀前药的共轭物或盐来治疗或预防癌症的方法。
• [EN] ARYL ETHER-BASE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASES DE TYPE ARYLÉTHER-BASE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2015038112A1

  公开（公告）日：2015-03-19

  The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.

  本公开涉及一般可抑制AAK1（适配器相关激酶1）的化合物，包括这些化合物的组合物，以及抑制AAK1的方法。
• [EN] PYRAZOLO[1,5-a]PYRIMIDINE-BASED COMPOUNDS, COMPOSITIONS COMPRISING THEM, AND METHODS OF THEIR USE<br/>[FR] COMPOSÉS À BASE DE PYRAZOLO[1,5-A] PYRIMIDINE, COMPOSITIONS LES COMPRENANT ET UTILISATIONS DE CEUX-CI
  申请人：LEXICON PHARMACEUTICALS INC

  公开号：WO2013134228A1

  公开（公告）日：2013-09-12

  Pyrazolo[1,5-a]pyrimidine-based compounds of the formula: are disclosed, wherein R1, R2 and R3 are defined herein. Compositions comprising the compounds and methods of their use to treat, manage and/or prevent diseases and disorders mediated by mediated by adaptor associated kinase 1 activity are also disclosed.

  基于吡唑并[1,5-a]嘧啶的化合物的公式如下：其中R1、R2和R3在此处被定义。还公开了包含这些化合物的组合物以及它们的使用方法，用于治疗、管理和/或预防由适配器相关激酶1活性介导的疾病和紊乱。
• PYRIMIDINYL AND 1,3,5-TRIAZINYL BENZIMIDAZOLES AND THEIR USE IN CANCER THERAPY
  申请人：Rewcastle Gordon William

  公开号：US20110009405A1

  公开（公告）日：2011-01-13

  Provided herein are pyrimidinyl and 1,3,5-triazinyl benzimidazoles of Formula I, and their pharmaceutical compositions, preparation, and use as agents or drugs for cancer therapy, either alone or in combination with radiation and/or other anticancer drugs.

  本文提供了式I的嘧啶基和1,3,5-三嗪基苯并咪唑化合物，以及它们的药物组合物、制备方法，以及作为抗癌治疗药物或药剂的用途，可以单独使用，也可以与放疗和/或其他抗癌药物联合使用。
• 3-Aminocyclopentanecarboxamides as modulators of chemokine receptors
  申请人：Xue Chu-Biao

  公开号：US20060004018A1

  公开（公告）日：2006-01-05

  The present invention is directed to compounds of Formula I: which are modulators of chemokine receptors. The compounds of the invention, and compositions thereof, are useful in the treatment of diseases related to chemokine receptor expression and/or activity.

  本发明涉及以下式的化合物： 这些化合物是趋化因子受体的调节剂。本发明的化合物及其组合物在治疗与趋化因子受体表达和/或活性相关的疾病方面是有用的。

表征谱图