53164-05-9

• 常用中文名：阿西美辛
• 常用英文名：acemetacin
• CAS号：53164-05-9
• 分子式：C₂₁H₁₈ClNO₆
• 分子量：415.824
• 相关类别： 原料药 解热镇痛药 非甾抗炎药
• 发布时间：2018-06-14 17:40:10
• 更新时间：2024-01-02 07:41:42
• Acemetacin是非甾体抗炎类化合物。

名称

• 中文名: 阿西美辛
• 英文名: acemetacin
• 中文别名: [1-(对氯苯甲酰基)-5-甲; [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-(4-氯苯甲酰基)-5-甲氧基-2-甲基-1H-吲哚-3-乙酸羧甲酯; 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-甲基吲哚-3-乙酸羧甲基酯; 炎痛美新
• 英文别名: ({[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl}oxy)acetic acid; 1H-Indole-3-acetic acid, 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-, carboxymethyl ester; Solart; 1-(4-Chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic Acid Carboxymethyl Ester; Acemetacinum; Tilur; [1-(4-Chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetoxyacetic Acid; glycolic acid ester of indomethacin; 1-(p-Chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid carboxymethyl ester; Reudol; Rheutrop; TVX-1322; BAY f4975; Acemetacin (JAN); acemetacin; Azeat; Acemix; aximeixin; {2-[1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetoxy}acetic acid; Acephlogont; [({1-[(4-chlorophenyl)carbonyl]-2-methyl-5-(methyloxy)-1H-indol-3-yl}acetyl)oxy]acetic acid; k-708; rheumibis; Rantudil; tv1322; Gamespir; [({1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetyl)oxy]acetic acid; Emflex; Acemetadoc; MFCD00151473; EINECS 258-403-4; Oldan

物化性质

• 密度: 1.4±0.1 g/cm3
• 沸点: 565.5±50.0 °C at 760 mmHg
• 熔点: 151.5°C
• 分子式: C₂₁H₁₈ClNO₆
• 分子量: 415.824
• 闪点: 295.8±30.1 °C
• 精确质量: 415.082275
• PSA: 94.83000
• LogP: 3.20
• 外观性状: 从石油醚得淡黄色细微结晶，熔点150-153℃。急性毒性LD50雄、雌小鼠，雄、雌大鼠(mg/kg)：55.5，18.42，24.2，30.1口服；34.1，51.1，38.1，28.3静脉注射。
• 蒸汽压: 0.0±1.6 mmHg at 25°C
• 折射率: 1.611
• 储存条件: -20°C Freezer
• 分子结构:

  1、 摩尔折射率：106.05

  2、 摩尔体积（cm³/mol）：305.4

  3、 等张比容（90.2K）：809.7

  4、 表面张力（dyne/cm）：49.4

  5、 极化率（10-24cm3）：42.04

• 计算化学:

  1.疏水参数计算参考值（XlogP）:无

  2.氢键供体数量:1

  3.氢键受体数量:6

  4.可旋转化学键数量:7

  5.互变异构体数量:无

  6.拓扑分子极性表面积94.8

  7.重原子数量:29

  8.表面电荷:0

  9.复杂度:620

  10.同位素原子数量:0

  11.确定原子立构中心数量:0

  12.不确定原子立构中心数量:0

  13.确定化学键立构中心数量:0

  14.不确定化学键立构中心数量:0

  15.共价键单元数量:1

• 更多:

  1.性状：从石油醚得淡黄色细微结晶。

  2.熔点：150-153℃。

生物活性

• 描述: Acemetacin是非甾体抗炎类化合物。
• 相关类别:
  研究领域 >> 炎症/免疫
• 靶点:

  COX-1:85 μM (IC50, in human intact cell)

• 参考文献:

  [1]. Tavares IA, et al. Non-steroidal anti-inflammatory drugs that cause relatively little gastric damage. J Gastroenterol Hepatol. 1998 Nov;13(S3):S190-S192.

MSDS

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 toxicR26/27/28 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 wordDanger Hazard statement(s) H300Fatal if swallowed. H310Fatal in contact with skin. H330Fatal if inhaled. Precautionary statement(s) P260Do not breathe dust/ fume/ gas/ mist/ vapours/ spray. P264Wash hands thoroughly after handling. P280Wear protective gloves/ protective clothing. P284Wear respiratory protection. P302 + P350IF ON SKIN: Gently wash with plenty of soap and water. P310Immediately call a POISON CENTER or doctor/ physician. Supplemental Hazardnone Statements Other hazards - none 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 ComponentClassificationConcentration Acemetacin CAS-No.53164-05-9Acute Tox. 1; Acute Tox. 2;<= 100 % EC-No.258-403-4H300, H310, H330 Hazardous ingredients according to Directive 1999/45/EC ComponentClassificationConcentration Acemetacin CAS-No.53164-05-9T+, 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 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 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 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. 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 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 +49 (0)6659 87300, 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. SECTION 9: Physical and chemical properties Information on basic physical and chemical properties a) AppearanceForm: solid b) Odourno data available c) Odour Thresholdno data available d) pHno data available e) Melting point/freezingno data available point f) Initial boiling point and no data available boiling range g) Flash pointno data available h) Evapouration rateno data available i) Flammability (solid, gas) no data available j) Upper/lowerno data available flammability or explosive limits k) Vapour pressureno data available l) Vapour densityno data available m) Relative densityno data available n) Water solubilityno data available o) Partition coefficient: n- no data available octanol/water p) Auto-ignitionno data available temperature q) Decompositionno data available temperature r) Viscosityno data available s) Explosive propertiesno data available t) Oxidizing propertiesno 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 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. 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. SECTION 14: Transport information UN number ADR/RID: 2811IMDG: 2811IATA: 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: 6.1IMDG: 6.1IATA: 6.1 Packaging group ADR/RID: IIIMDG: IIIATA: II Environmental hazards ADR/RID: noIMDG Marine pollutant: noIATA: no Special precautions for user no data available 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 H300Fatal if swallowed. H310Fatal in contact with skin. H330Fatal if inhaled. Full text of R-phrases referred to under sections 2 and 3 T+Very toxic R26/27/28Very 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.

毒性和生态

毒理学数据: 急性毒性LD50雄、雌小鼠，雄、雌大鼠(mg/kg)：55.5，18.42，24.2，30.1口服；34.1，51.1，38.1，28.3静脉注射。 CHEMICAL IDENTIFICATION RTECS NUMBER : NL3521400 CHEMICAL NAME : 1H-Indole-3-acetic acid, 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-, carboxymethyl ester CAS REGISTRY NUMBER : 53164-05-9 BEILSTEIN REFERENCE NO. : 0501672 LAST UPDATED : 199612 DATA ITEMS CITED : 24 MOLECULAR FORMULA : C21-H18-Cl-N-O6 MOLECULAR WEIGHT : 415.85 WISWESSER LINE NOTATION : T56 BNJ BVR& C1 D1VO1VQ GO1 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 24200 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 23 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 28400 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 28300 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 19300 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 18420 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 23300 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 22800 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 34100 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 27600 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 64200 ug/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 22,657,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 200 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >100 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - cat DOSE/DURATION : >600 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 300 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 194 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 192 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 280 mg/kg/35D-C TOXIC EFFECTS : Gastrointestinal - ulceration or bleeding from stomach Endocrine - other changes Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 22,665,1981 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 13500 ug/kg SEX/DURATION : female 17-22 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 22,777,1981 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 56 mg/kg SEX/DURATION : female 16-22 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - stillbirth REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 44 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Effects on Newborn - behavioral REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 22,765,1981 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 88 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Maternal Effects - uterus, cervix, vagina Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Newborn - live birth index (measured after birth) REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 22,765,1981 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 108 mg/kg SEX/DURATION : female 17-22 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Maternal Effects - parturition Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 22,777,1981 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 351 mg/kg SEX/DURATION : female 6-18 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - other developmental abnormalities REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1398,1980

安全

• 符号: GHS06
• 信号词: Danger
• 危害声明: H300 + H310 + H330
• 警示性声明: Missing Phrase - N15.00950417-P260-P262-P280-P302 + P352 + P310-P304 + P340 + P310
• 个人防护装备: Eyeshields;Faceshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges
• 危害码 (欧洲): T+:Verytoxic;
• 风险声明 (欧洲): R26/27/28
• 安全声明 (欧洲): S22-S25-S36/37/39-S45
• 危险品运输编码: UN 2811
• RTECS号: NL3521400
• 包装等级: II
• 危险类别: 6.1(a)
• 海关编码: 2942000000

合成路线

75302-98-6 ~77% 53164-05-9

文献：NitroMed, Inc. Patent: US2004/24057 A1, 2004 ; Location in patent: Page/Page column 52 ;

53164-04-8 ~95% 53164-05-9

文献：Gynther, Mikko; Ropponen, Jarmo; Laine, Krista; Leppaenen, Jukka; Haapakoski, Paula; Peura, Lauri; Jaervinen, Tomi; Rautio, Jarkko Journal of Medicinal Chemistry, 2009 , vol. 52, # 10 p. 3348 - 3353

19501-58-7 ~% 53164-05-9

文献：Arzneimittel-Forschung/Drug Research, , vol. 30, # 8 A p. 1314 - 1325

53164-08-2 ~% 53164-05-9

文献：Arzneimittel-Forschung/Drug Research, , vol. 30, # 8 A p. 1314 - 1325

53-86-1 ~% 53164-05-9

文献：Arzneimittel-Forschung/Drug Research, , vol. 30, # 8 A p. 1314 - 1325

123-76-2 ~% 53164-05-9

文献：Arzneimittel-Forschung/Drug Research, , vol. 30, # 8 A p. 1314 - 1325

53164-03-7 ~% 53164-05-9

文献：Arzneimittel-Forschung/Drug Research, , vol. 30, # 8 A p. 1314 - 1325

上下游产品

上游产品  5
75302-98-6 19501-58-7 53-86-1 123-76-2
53164-03-7
下游产品  0

制备

方法1：以在吲哚美辛的合成中得到的N-(4-甲氧基苯基)-4-氯苯甲酰肼为原料，和(3-乙酰基丙酰氧基)乙酸苄酯(其制备见方法3)环合，得到[1-(4-氯苯甲酰基)-5-甲氧基-2-甲基-1H-吲哚-3-乙酰氧基]乙酸苄酯(I)。得到的苄酯(I)溶于冰醋酸中，在室温下在钯-炭催化剂上进行加氢，当氢吸收停止后，过滤去催化剂，滤液减压浓缩，残液加入石油醚中重结晶，得阿西美辛精品，熔点149.5～150.5℃，收率93%。
方法2：以吲哚美新为原料。
在搅拌下，将180g(0.503mo1)吲哚美新溶于900ml无水二甲基甲酰胺，加入35g(0.253mo1)磨细和干燥的碳酸钾，在50℃下搅拌45min。在15min中，滴入128g(0.56mo1)溴乙酸苄酯，在50℃下搅拌3h。过滤，滤液浓缩，剩余物溶于氯仿，用水洗至中性，无水硫酸钠干燥。浓缩，异丙醚-乙酸乙酯重结晶，得228g化合物(I)，收率89.5%，熔点96℃。
60g(0.12mo1)化合物(I)溶于700ml乙酸乙酯，加入6g 5%钯-炭催化剂，在40℃下氢化1h，吸收约2.921L氢气(20℃)。过滤，浓缩，往剩余物加入石油醚(40～60℃)，使结晶完全，并在冰箱中放置12h。过滤，先空气中干燥，后真空干燥，得46g阿西美辛，收率93%，熔点150～153℃。
方法3：以对甲氧基苯肼和(3-乙酰基丙酰氧基)乙酸苄酯为原料。(3-乙酰基丙酰氧基)乙酸苄酯的制备。93.5g(0.68mo1)干燥碳酸钾悬浮于650ml无水二甲基甲酰胺，加热至40℃，在70min内滴入116.1g(1.0mo1)3-乙酰基丙酸。加毕，冷至30℃，加入229.1g(1.0mo1)2-溴乙酸苄酯。在50℃下反应4h。过滤除去无机盐，用甲苯提取。提取液浓缩，剩余物溶于400ml二氯甲烷，水洗至中性，无水硫酸钠干燥。浓缩，剩余物溶于。1000ml异丙醚，加入冷至-25℃的1500ml石油醚(40～60℃)，于-15℃下放置1h。过滤，在22℃下真空干燥，得235g(3-乙酰基丙酰氧基)乙酸苄酯，收率89%，熔点31.5～32.5℃，沸点176～178℃/1.20kPa。
26.3g(0.19mo1)对甲氧基苯肼溶于125ml冰乙酸和450ml水，在搅拌下，滴入50g(0.19mo1)(3-乙酰基丙酰氧基)乙酸苄酯，再搅拌1h。用甲苯提取，提取液水洗至中性，干燥，浓缩，得75.5g棕色油状的化合物(Ⅱ)，直接用于下列反应。
将化合物(Ⅱ)直接溶于125ml无水吡啶，加入500ml无水乙醚，再在0℃加入43.5g对氯苯甲酰氯在250ml无水乙醚的溶液，在氮气保护下回流2h，冷却，水洗至中性，干燥，浓缩，得95g化合物(Ⅲ)的粗品。无需提纯，直接用于下步反应。
将化合物(Ⅲ)直接溶于380ml乙酸，在80℃下加热5min。减压浓缩，剩余物溶于氯仿，用碳酸氢钠溶液洗，并水洗至中性。用氧化铝层析，氯仿洗脱。浓缩后用乙醚重结晶，得10.6g化合物(I)。从对甲氧基苯肼计，收率11%。化合物(I)再如方法2还原为阿西美辛。

方法4：对甲氧基苯肼和(3-乙酰基丙酰氧基)乙酸苄酯也可先环合，再对氯苯甲酰化。
45.7g(0.26mo1)对甲氧基苯肼盐酸盐和69.2g(0.26mo1)(3-乙酰基丙酰氧基)乙酸苄酯溶于260ml乙酸，先在28℃搅拌42h，再在50℃搅拌5h。蒸出150～180ml溶剂后，加入500ml冰水，用4×100ml甲苯提取。提取液合并，用碳酸氢钾溶液洗至无酸，无水硫酸钠干燥。过滤，浓缩，得92g粗品。经蒸馏，可得76g化合物(IV)，收率80%，沸点165℃(≤100Pa)。
77.5g(0.44mo1)对氯苯甲酰氯溶于275ml专用石油(沸点180~220℃)中加热至沸，在20min中，滴加41g(0.1lmo1)化合物(Ⅳ)。加毕，在190-195℃加热2～3h，至无氯化氢放出。冷至40℃，加入200ml乙醚。在室温下结晶后，再放入冰箱过夜。过滤收集结晶，用异丙醚洗，再用乙酸乙酯和异丙醚重结晶，得43.3g化合物(I)，收率78%。化合物(I)再如方法2还原为阿西美辛。

海关

海关编码	2933990090
中文概述	2933990090. 其他仅含氮杂原子的杂环化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:20.0%
申报要素	品名, 成分含量, 用途, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期
Summary	2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%